In drug discovery, approximately 70% of new drug candidates have shown poor aqueous solubility
in recent years. Currently, approximately 40% of the marketed immediate release (IR) oral drugs are
categorized as practically insoluble (<100 g/mL). The aqueous solubility of a drug is a critical determinant
of its dissolution rate. The Biopharmaceutics Classification System (BCS) is a useful tool for decisionmaking
in formulation development from a biopharmaceutical point of view. BCS Class II drugs are
identified as low solubility and high permeability. In general, the bioavailability of a BCS Class II drug is
rate limited by its dissolution so that even a small increase in dissolution rate sometimes results in a large
increase in bioavailability. Therefore, an enhancement of the dissolution rate of the drug is thought to be
a key factor for improving the bioavailability of BCS Class II drugs. Solid lipid nanoparticles (SLNs)
were developed in the mid-1980s as an alternative system to the existing traditional carriers (emulsions,
liposomes, microparticles, and their polymeric counterparts) when Speiser prepared the first micro- and
nano-particles (named nano pellets) made up of solid lipids for oral administration. SLNs are colloidal
carriers made up of lipids that remain solid at room temperature and body temperature and also offer unique
properties such as small size (50–500 nm), large surface area, high drug loading, and the interaction of
phases at the interfaces and are attractive for their potential to improve performance of pharmaceuticals,
nutraceuticals, and other materials. Moreover, SLN are less toxic than other nanoparticulate systems
due to their biodegradable and biocompatible nature. SLN is capable of encapsulating hydrophobic
and hydrophilic drugs, and they also provide protection against chemical, photochemical, or oxidative
degradation of drugs, as well as the possibility of a sustained release of the incorporated drugs.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Friends..me and my best buddy miss.pragya paramita pal prepared this presentation during the last semester of our graduation.I am just uploading this so that this can help you to prepare better presentations based on such topics.Thanks to my guide and my friend miss.pragya.Enjoy friends & best of luck..
Polymer microspheres for controlled drug releaseDuwan Arismendy
Polymer microspheres can be employed to deliver medication in a rate-controlled and sometimes targeted manner. Medication is released from a microsphere by drug leaching from the polymer or by degradation of the polymer matrix. Since the rate of drug release is controlled by these two factors, it is important to understand the physical and chemical properties of the releasing medium. This review presents the methods used in the preparation of microspheres from monomers or from linear polymers and discusses the physio-chemical properties that affect the formation, structure, and morphology of the spheres. Topics including the effects of molecular weight, blended spheres, crystallinity, drug distribution, porosity, and sphere size are discussed in relation to the characteristics of the release process. Added control over release profiles can be obtained by the employment of core-shell systems and pH-sensitive spheres; the enhancements presented by such systems are discussed through literature examples.
Hydrogels,
introduction,
historical background,
properties,
classification,
difference between chemical and physical hydrogels,
common uses,
pharmaceutical applications,
preparation methods,
list of monomers used,
analytical machines,
advantages,
disadvantages,
conclusion
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Friends..me and my best buddy miss.pragya paramita pal prepared this presentation during the last semester of our graduation.I am just uploading this so that this can help you to prepare better presentations based on such topics.Thanks to my guide and my friend miss.pragya.Enjoy friends & best of luck..
Polymer microspheres for controlled drug releaseDuwan Arismendy
Polymer microspheres can be employed to deliver medication in a rate-controlled and sometimes targeted manner. Medication is released from a microsphere by drug leaching from the polymer or by degradation of the polymer matrix. Since the rate of drug release is controlled by these two factors, it is important to understand the physical and chemical properties of the releasing medium. This review presents the methods used in the preparation of microspheres from monomers or from linear polymers and discusses the physio-chemical properties that affect the formation, structure, and morphology of the spheres. Topics including the effects of molecular weight, blended spheres, crystallinity, drug distribution, porosity, and sphere size are discussed in relation to the characteristics of the release process. Added control over release profiles can be obtained by the employment of core-shell systems and pH-sensitive spheres; the enhancements presented by such systems are discussed through literature examples.
Hydrogels,
introduction,
historical background,
properties,
classification,
difference between chemical and physical hydrogels,
common uses,
pharmaceutical applications,
preparation methods,
list of monomers used,
analytical machines,
advantages,
disadvantages,
conclusion
Abstract
Niosomes, non-ionic surfactant vesicles (NSVs), are the hydrated lipids composed mainly of different classes of non-ionic surfactants, introduced in the seventies as a cosmetic vehicle. Nowadays, niosomes are used as important new drug delivery systems by many research groups and also they are effective immunoadjuvants which some commercial forms are available in the market. These vesicles recently used as gene transfer vectors as well. This review article presents a brief report about the achievements in the field of nanoscience related to NSVs. Different polar head groups from a vast list of various surfactants with one, two or three lipophilic alkyl, perfluoroalkyl and steroidal moieties may be utilized to form the proper vesicular structures for encapsulating both hydrophilic and hydrophobic compounds. The methods of niosome preparation, the vesicle stability related aspects and many examples of pharmaceutical applications of NSVs will be presented. The routes of administration of these amphiphilic assemblies are also discussed.
Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids, and may exist as ultrafine vesicular, micellar, or hexagonal aggregates, depending on the chemical structure of drug-lipid complex.
novel drug delivery system is a system that uses different carriers to deliver the drug to the specific site of action , here is a presentation that discuss the types of carrier and their
pharmaceutical application
Done by: Faten Al-Sadek , Pharmacy student at Mohammed Al-Mana college for Health Sciences -MACHS
Polymer-drug conjugates are a novel class of nanocarriers for drug delivery, which can protect the drug from premature degradation, prevent the drug from premature interaction with the biological environment and enhance the absorption of the drugs into tissues (by enhanced permeability and retention effect or active targeting).
Polymer-drug conjugates are often considered as new chemical entities (NCEs) owing to a distinct pharmacokinetic profile from that of the parent drug.
Conjugation of a drug with a polymer forms so-called ‘Polymeric Prodrug’.
Sustained drug delivery systems significantly improve therapeutic efficacy of drugs. Drug-release-retarding polymers are the key performers in sustained release drug delivery system for which various natural, semi-synthetic and synthetic polymeric materials have been investigated. Besides this several polymers are often utilized in the design of novel drug delivery systems such as those that target delivery of the drug to a specific region in the gastrointestinal tract or in response to external stimuli to release the drug.
INTRODUCTION TO BIOPHARMACEUTICS & ABSORPTION Ram Kanth
Greetings!
Good Day to All..
This presentation is all about the Introduction of Biopharmaceutics and Absorption.
The detailed discussion about the various definitions in relation to Biopharmaceutics. Also it includes the introduction to Absorption of drug, Plasma drug Conc. Vs Time Profile and about Cell membrane - its structure and functions.
Your suggestion and comments are welcome for further improvement in my presentations.
Thank you all for your valuable time.
Disclaimer Note: Some contents in the presentation were taken from online sources which is purely used for education purpose and for any personal financial or commercial aspects. I thank all the source providers in online for your efforts and support in sharing of knowledge.
“Microparticles are defined as particulate dispersions or solid particles with a size in the range of 1-1000 μm.”
The drug is dissolved, entrapped, encapsulated or attached to a microparticle matrix.
Abstract
Niosomes, non-ionic surfactant vesicles (NSVs), are the hydrated lipids composed mainly of different classes of non-ionic surfactants, introduced in the seventies as a cosmetic vehicle. Nowadays, niosomes are used as important new drug delivery systems by many research groups and also they are effective immunoadjuvants which some commercial forms are available in the market. These vesicles recently used as gene transfer vectors as well. This review article presents a brief report about the achievements in the field of nanoscience related to NSVs. Different polar head groups from a vast list of various surfactants with one, two or three lipophilic alkyl, perfluoroalkyl and steroidal moieties may be utilized to form the proper vesicular structures for encapsulating both hydrophilic and hydrophobic compounds. The methods of niosome preparation, the vesicle stability related aspects and many examples of pharmaceutical applications of NSVs will be presented. The routes of administration of these amphiphilic assemblies are also discussed.
Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids, and may exist as ultrafine vesicular, micellar, or hexagonal aggregates, depending on the chemical structure of drug-lipid complex.
novel drug delivery system is a system that uses different carriers to deliver the drug to the specific site of action , here is a presentation that discuss the types of carrier and their
pharmaceutical application
Done by: Faten Al-Sadek , Pharmacy student at Mohammed Al-Mana college for Health Sciences -MACHS
Polymer-drug conjugates are a novel class of nanocarriers for drug delivery, which can protect the drug from premature degradation, prevent the drug from premature interaction with the biological environment and enhance the absorption of the drugs into tissues (by enhanced permeability and retention effect or active targeting).
Polymer-drug conjugates are often considered as new chemical entities (NCEs) owing to a distinct pharmacokinetic profile from that of the parent drug.
Conjugation of a drug with a polymer forms so-called ‘Polymeric Prodrug’.
Sustained drug delivery systems significantly improve therapeutic efficacy of drugs. Drug-release-retarding polymers are the key performers in sustained release drug delivery system for which various natural, semi-synthetic and synthetic polymeric materials have been investigated. Besides this several polymers are often utilized in the design of novel drug delivery systems such as those that target delivery of the drug to a specific region in the gastrointestinal tract or in response to external stimuli to release the drug.
INTRODUCTION TO BIOPHARMACEUTICS & ABSORPTION Ram Kanth
Greetings!
Good Day to All..
This presentation is all about the Introduction of Biopharmaceutics and Absorption.
The detailed discussion about the various definitions in relation to Biopharmaceutics. Also it includes the introduction to Absorption of drug, Plasma drug Conc. Vs Time Profile and about Cell membrane - its structure and functions.
Your suggestion and comments are welcome for further improvement in my presentations.
Thank you all for your valuable time.
Disclaimer Note: Some contents in the presentation were taken from online sources which is purely used for education purpose and for any personal financial or commercial aspects. I thank all the source providers in online for your efforts and support in sharing of knowledge.
“Microparticles are defined as particulate dispersions or solid particles with a size in the range of 1-1000 μm.”
The drug is dissolved, entrapped, encapsulated or attached to a microparticle matrix.
A Novel Drug Delivery System (NDDS) can be defined as a new approach that combines innovative development, formulations, new technologies, novel methodologies for delivering pharmaceutical compounds in the body as needed to safely achieve its desired pharmacological effects
Meirelles LMA, Andrade AWL. Rifampicinand technologies employed in improving its dissolutionprofile. Boletim Informativo Geum. 2014 out/dez; 5(4): 60-67. URL
http://www.ojs.ufpi.br/index.php/geum/article/view/3514/2838
Rifampicin is an antibiotic of the group of naphtalenics ansamicins, produced by Streptomyves mediterranei. This drug was discovered in the 60's, with bactericidal activity about 95% of sensitive strains of Mycobacterium tuberculosis and Mycobacterium leprae, the etiologic agents of tuberculosis and leprosy, respectively. Investigations have shown that the main limitation of some formulations of rifampicin is due to their low solubility in aqueous medium, which fits in class II Biopharmaceutical Classification System. Objective: In this regard, the objective of this review was to demonstrate the main techniques used to optimize the dissolution profile of the drug rifampin. Methods: The scientific review was developed by database search Pub Med, Science direct, Scopus, CAPES Periodicals and ACS Publications, using the keywords rifampicin, release system, dissolution and their associations in the period March to June 2014 in documents published in the year 1971 to 2013. Results: Scientific Publications show that the restricted solubility of this compound can be circumvented by delivery systems for non-conventional, such as vesicular systems, inclusion complexes or solid dispersions. Conclusion: These technologies allow for pharmaceutical forms more stable and soluble bioavailability less variable.
Solid lipid nanoparticles (SLN) are most developing
formulations of nanotechnology with several applications in different fields like drug delivery, clinical medicine and research as well as in other varied sciences. SLN are defined as the spherical particles of nanometer range which immersed in water or aqueous surfactant solution either using lipophilic and hydrophilic drug. Solid lipid nanoparticle technology represents a promising new approach to lipophilic drug delivery.
The main objective of present investigation is to formulate the floating tablets of
Ranitidine.HCl using 32 factorial design. Ranitidine.HCl, H2-receptor antagonist belongs to
BCS Class-III. The Floating tablets of Ranitidine.HCl were prepared employing different
concentrations of HPMCK4M and Guar Gum in different combinations as a release rate
modifiers by Direct Compression technique using 32 factorial design. The concentration of
Polymers , HPMCK4M and Guar Gum required to achieve desired drug release was selected
as independent variables, X1 and X2 respectively whereas, time required for 10% of drug
dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables.
Totally nine formulations were designed and are evaluated for hardness, friability, thickness,
% drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all
the formulation were found to be within the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the
statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated.
Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed
polynomial equations were verified by designing 2 check point formulations(C1, C2).
According to SUPAC guidelines the formulation (F5) containing combination of 22.5%
HPMCK4M and 22.5% Guar Gum, is the most similar formulation (similarity factor f2=85.01,
dissimilarity factor f1= 15.358 & No significant difference, t= 0.169) to marketed product
(ZANTAC). The selected formulation (F5) follows Higuchi’s kinetics, and the mechanism of
drug release was found to be Non-Fickian Diffusion (n= 0.922).
Novel Drug Delivery System An OverviewYogeshIJTSRD
In present scenario evolution of an existing drug molecule from a old form to a novel delivery system can significantly improve its performance in terms of patient compliance, safety and efficacy. In the form of a control drug delivery system an existing drug molecule can get a new life. An appropriately designed Novel Drug Delivery System can be a major advance for solving the problems related towards the release of the drug at specific site with specific rate. The porpuse for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery system. This article covers the basic information regarding Novel Drug Delivery Systems and also advantages, factor etc. Chiranjit Barman | Dr. Gaurav Kumar Sharma | Dr. Kausal Kishore Chandrul "Novel Drug Delivery System: An Overview" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45068.pdf Paper URL: https://www.ijtsrd.com/pharmacy/novel-drug-delivery-sys/45068/novel-drug-delivery-system-an-overview/chiranjit-barman
Biopharmaceutics Presentation - A brief presentation on the topic- BCS Classification and it's role in formulation development . Includes uses of BCS Classification
2.Sagar Goda Biological classification system (BCS); its significance on diss...Sagar Goda
This presentation provides a detailed information about Biopharmaceutics classification system(BCS) and its significance on dissolution study as well as its application in dosage form development.
Similar to Solid Lipid Nanoparticles: A Strategy to Improve Oral Delivery of the Biopharmaceutics classification system (BCS) Class II Drugs (20)
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
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Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
2. Kumar, et al.: Solid Lipid Nanoparticles: A Strategy to Improve Oral Delivery of BCS Class II Drugs
IJPBA/Oct-Dec-2018/Vol 9/Issue 4 205
The BCS categorizes drug substances into one
of the four categories based on their solubility
and intestinal permeability, and these four
categories are defined as follows: High solubility/
high permeability (Class
I), low solubility/
high permeability (Class II), high solubility/low
permeability (Class
III), and low solubility/low
permeability (Class IV).
For BCS Class
I or III drugs, formulations are
designed with a simple strategy. However, for
BCS Class II or IV drugs, deliberate formulation
designs based on both the physicochemical and
biopharmaceutical properties of the drugs are
required to obtain sufficient and reproducible
bioavailability after oral administration. The
viable formulation options based on the BCS are
summarized in Figure 1.
FORMULATIONS FOR BCS CLASS II
DRUGS
The molecular characteristics of BCS Class
II
drugs are identified as low solubility and
high permeability. For instance, cyclosporine,
griseofulvin, and itraconazole are categorized into
this class.[5]
In general, the bioavailability of a
BCS Class II drug is rate limited by its dissolution
so that even a small increase in dissolution
rate sometimes results in a large increase in
bioavailability.[6]
Therefore, an enhancement of
the dissolution rate of the drug is thought to be
a key factor for improving the bioavailability of
BCS Class II drugs.
Several physicochemical factors control the
dissolution rate of the drugs. According to the
modification of the Noyes–Whitney equation,
the factors affecting the drug dissolution rate are
defined as the effective surface area, diffusion
coefficient, diffusion layer thickness, saturation
solubility, amount of dissolved drug, and volume
of dissolution media.[3]
Increases in the saturation
solubility and the effective surface area have a
positive impact on the dissolution rate of the drugs,
and these factors could be increased by efforts of
pre-formulation study and formulation design.
Various approaches to overcome the poor aqueous
solubilityofdrugcandidateshavebeeninvestigated
in drug research and development. Changing
the chemical structure in the lead optimization
phase is considered to be an option to increase the
solubility of drug candidates. Prodrug approaches
might also enhance the aqueous solubility of drug
candidates by introducing a polar functional group
into the structure of a molecule.[7]
In recent years, it has become more and more
evident that the development of new drugs
alone is not sufficient to ensure progress in drug
therapy. Exciting experimental data obtained in
vitro are very often followed by disappointing
results in vivo. Main reasons for the therapy
failure include insufficient drug concentration
due to poor absorption, rapid metabolism and
elimination (e.g.,
peptides and proteins), drug
distribution to other tissues combined with high
drug toxicity (e.g.,
cancer drugs), poor drug
solubility which excludes i.v. injection of aqueous
drug solution, and high fluctuation of plasma
levels due to unpredictable bioavailability after
peroral administration, including the influence
of food on plasma levels (e.g., cyclosporine).[8]
A
Figure 1: The Biopharmaceutics Classification System and viable formulation options
3. Kumar, et al.: Solid Lipid Nanoparticles: A Strategy to Improve Oral Delivery of BCS Class II Drugs
IJPBA/Oct-Dec-2018/Vol 9/Issue 4 206
promising strategy to overcome these problems
involves the development of suitable drug
carrier systems. The in vivo fate of the drug is no
longer mainly determined by the properties of
the drug but by the carrier system, which should
permit a controlled and localized release of the
active drug according to the specific needs of
the therapy.[9]
The size of the carrier depends on
the desired route of administration and ranges
from few nanometers (colloidal carriers) to
the micrometer range (microparticles) and to
several millimeters (implants). Implants and
microparticles are too large for drug targeting and
intravenous administration. Therefore, colloidal
carriers have attracted increasing attention
during recent years
[10,11]
Investigated systems
include nanoparticles, nanoemulsions, liposomes,
nanosuspensions, micelles, and soluble polymer–
drug conjugates. Polymers from natural[11,12]
and
synthetic sources[13]
have been used. Polymer-
based systems in the submicron size range include
water-soluble polymer-drug conjugates,[14]
polymer nanocapsules, and nanospheres.[15]
Problems of polymer-based nanoparticles derive
from residues from organic solvents used in the
production process, polymer cytotoxicity, and the
scaling up of the production processes.[16]
Liposomes are spherical vesicles composed
of one or more phospholipid bilayers (in most
cases phosphatidylcholine). Lipophilic drugs
can be incorporated into the lipid bilayers while
hydrophilic drugs are solubilized in the inner
aqueous core.[17]
Drug release, in vivo stability,
and biodistribution are determined by size, surface
charge, surface hydrophobicity, and membrane
fluidity.[18]
Nanosuspensions are colloidal particles
which are composed of the drug and the emulsifier
only. Possible production procedures include ball
milling or high-pressure homogenization (HPH).[19]
Lipid nanoemulsions were introduced during the
50s for the purpose of parenteral nutrition. Fatty
vegetable oils (e.g.,
soy oil) or middle chain
triglycerides are used for the lipid phase, which
amounts to typically 10–20% of the emulsion.
Further ingredients include phospholipids
(stabilizers, 0.6–1.5%) and glycerol (osmolarity
regulation,2.25%). During recentyears, it has been
recognized that these systems might also be used
as drug carriers for lipophilic drugs and several
formulations are commercialized. The possibility
of controlled drug release from nanoemulsions is
limited due to the small size and the liquid state of
the carrier.[20]
The use of solid lipids instead of liquid oils is a
very attractive idea to achieve controlled drug
release, because drug mobility in a solid lipid
should be considerably lower compared with a
liquid oil. Nanopellets developed by Speiser[21]
were produced by dispersing of melted lipids with
high-speed mixers or ultrasound. The products
obtained by this procedure often contain relatively
high amounts of microparticles. This might not
be a serious problem for peroral administration,
but it excludes an intravenous injection. Higher
concentrations of the emulsifier not only result in
a reduction of the particle size but also increase
the risk of toxic side effects. In the following
years, it has been demonstrated that HPH is a more
effective method for the production of submicron-
sized dispersions of solid lipids compared to high
shear mixing or ultrasound.[22]
Most solid lipid
nanoparticle (SLN) dispersions produced by
HPH are characterized by an average particle size
below 500 nm and a low microparticle content.
Other production procedures are based on the use
of organic solvents (HPH solvent evaporation) or
on dilution of microemulsions.[23]
SLN
SLNs [Figure 2] were developed in the mid-1980s
as an alternative system to the existing traditional
carriers (emulsions, liposomes, microparticles,
and their polymeric counterparts) when Speiser
prepared the first micro- and nano-particles
(namednanopellets)madeupofsolidlipidsfororal
administration.[24]
SLNs avoid some of their major
disadvantages such as cytotoxicity of polymers
and the lack of a suitable large-scale production
method for polymeric nanoparticles.[16]
SLNs are
colloidal carriers made up of lipids that remain
Figure 2: Schematic representation of solid lipid
nanoparticle dispersion stabilized with surfactant molecules
showing entrapment of drug
4. Kumar, et al.: Solid Lipid Nanoparticles: A Strategy to Improve Oral Delivery of BCS Class II Drugs
IJPBA/Oct-Dec-2018/Vol 9/Issue 4 207
solid at room temperature and body temperature
and also offer unique properties such as small size
(50–500 nm),largesurfacearea,highdrugloading,
and the interaction of phases at the interfaces
and are attractive for their potential to improve
performance of pharmaceuticals, nutraceuticals,
and other materials.[23]
Moreover, SLN is less
toxic than other nanoparticulate systems due to
their biodegradable and biocompatible nature.
SLN is capable of encapsulating hydrophobic and
hydrophilic drugs, and they also provide protection
against chemical, photochemical, or oxidative
degradation of drugs, as well as the possibility of
a sustained release of the incorporated drugs.[25]
SLN is colloidal particles composed of
biocompatible/biodegradable lipid matrix that is
solidatbodytemperatureandexhibitssizeinarange
of 100–400
nm. SLN offers several advantages
such as controlled drug release, targeted delivery,
increased drug stability, high drug payload, least
biotoxicity, large-scale production, and ease of
sterilization. General ingredients used in the
preparation of SLN are solid lipid(s), emulsifier(s),
and water. The term -lipid has a broader sense
here and includes triglycerides (e.g.,
tristearin),
fatty acids (e.g.,
stearic acid), partial glycerides
(e.g.,
Imwitor), steroids (e.g.,
cholesterol), and
waxes (e.g., cetyl palmitate).[26]
AnewerversionofSLNcallednanostructuredlipid
carriers (NLC), with increased drug loading, is
also becoming popular recently for brain targeting
which is composed of a solid lipid and a certain
amount of liquid lipid (oil), maintaining the solid
state at both room and body temperatures.[27]
Some other properties of lipid nanoparticles
are the drug pseudo-zero order kinetics, the
prolonged/sustained/controlled release obtained
in vitro for drugs incorporated in SLN (depending
on the surface properties), their rapid uptake
(internalization) by cell lines (5–10
min), and
also the possibility of preparation of stealth
SLN using PEG molecules so as to avoid the
reticuloendothelial system.[24]
Moreover, the possibility of loading drugs with
differing physicochemical and pharmacological
properties, no requirement of specialized
instruments/apparatuses, and preparation without
the use of organic solvents (in some methods
like self- emulsification and HPH) make SLNs a
highly versatile delivery system. Altering surface
characteristics by coating SLN with hydrophilic
molecules improves plasma stability and
biodistribution, and subsequent bioavailability of
drugs entrapped.[28]
Advantages of SLNs[25,29]
1. Controlled and targeted drug release.
2. Possible high drug loading.
3. Feasibility of carrying both hydrophilic and
lipophilic drugs.
4. Water-based formulation avoids organic
solvents.
5. Physiological lipids decrease the prevalence
of acute or chronic toxicity; no reported
biotoxicity of the carrier system.
6. Improved drug stability.
7. Most lipids being biodegradable, SLNs have
excellent biocompatibility.
8. Less expensive than polymeric or surfactant-
based carriers.
9. Easy to scale up and sterilize.
10. Easy to validate.
11. Easy to gain regulatory approval.
Disadvantages of SLNs
1. Poor drug loading capacity of drugs having
limited solubility in lipid melt.
2.
Relatively very high water content of
dispersions (70–99.9%).
3. Drug expulsion after polymeric transition
during storage.
The drug loading capacity of conventional SLNs
is depended on the following factors:
• Solubility of the drug in lipid melts
• Structure of the lipid matrix
• Polymorphic state of the lipid matrix.
Advanced forms of SLN
NLCs
NLCs, introduced at the turn of the millennium,
represent a new and improved generation of SLNs
and are made of a solid lipid matrix entrapping
liquid-lipid nano-compartments, the blend being
solid at body temperature. This new generation of
lipid carriers (NLCs) was introduced to overcome
the problems associated with SLNs, such as
limited drug loading capacity, drug expulsion
during storage and adjustment of drug release,
and long-term physical stability of the suspension.
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Production procedures are identical for both lipid
particles, SLNs and NLCs.[30]
Lipid drug conjugates
Lower drug loading capacity of hydrophilic actives
was a major issue in SLNs due to partitioning
effects during the production process. Highly
potent low-dose drugs can be suitably incorporated
only in the solid lipid matrix.[31]
Polymer lipid hybrid nanoparticles (PLNs)
PLNs hold great promise as a drug delivery vehicle
in the treatment of a myriad of diseases such as
breast cancer. A
PLN comprises three distinct
functional components:
• Hydrophobic polymeric core to encapsulate
poorly water-soluble drugs.
• Hydrophilic polymeric shell to enhance PLN
stability and circulation half-life.
• Lipid monolayer at the core and shell interface
to promote drug retention inside the polymeric
core.[32]
General excipients used for SLN
production[32,26]
The general ingredients used for the preparation of
SLNs are solid lipid(s) with relatively low melting
points (solid at room and body temperature),
emulsifier(s), and water. An overview of
excipients, which are commonly used for SLNs, is
listed here with few examples.
• Lipids (Triacylglycerols): Tricaprin, Trilaurin,
Trimyristin, Tripalmitin, Tristearin, etc..
• Hard fats: Witepsol™ (W/H 35, H42, E85)
• Acylglycerols: Glyceryl behenate (Gelucire
50/02, 50/13, 44/14), Glycerol monostearate
(Imwitor 900™), Glyceryl behenate
tribehenate (Compritol 888 ATO™), Glycerol
Palmitostearate(PrecirolATO5™),CutinaCBS,
Glyceryl tripalmitate (Dynasan® 116), Glyceryl
trimyristin (Dynasan® 114), Cetyl palmitate,
Glyceryl tristearin (Dynasan 118), etc.
• Fatty acids: Stearic acid, palmitic acid,
decanoic acid, behenic acid, etc.
• Waxes: Cetyl palmitate
• Others: Hydrogenated coco-glycerides,
Softisan 154.
Surfactant/Co-emulsifier•phospholipids:Soybean
lecithin, egg lecithin, phosphatidylcholine
• Ethylene/propylene oxide copolymer:
Polaxomer 188, 182, 407, 908
• Sorbitan ethylene/propylene oxide copolymer:
Polysorbate 20, 60, 80
• Alkylaryl polyether alcohol polymer:
Tyloxapol
• Bile salts: Sodium cholate, glycocholate,
taurocholate, taurodeoxycholate
• Alcohols/acids: Butanol, butyric acid, ethanol,
poly vinyl alcohol
• Others: Hydroxypropyl distarch, tegocare,
epikuron 200, etc.
Production methods for SLNs (HPH
technique)
Hot homogenization technique
In this technique, lipids are forced through a
narrow gap (few micron ranges) with high pressure
(100–200bars).Disruptionofparticlesintosubmicron
range occurs due to the shear stress and cavitation
(due to a sudden decrease in pressure) force. There
are two approaches - hot and cold homogenization
techniques. For both the techniques, a common
preparatory step involves the drug incorporation into
the bulk lipid by dissolving/dispersing/solubilizing
the drug in the lipid being melted at approximately
5–10°C above the melting point.[27]
The melted lipid-containing drug is dispersed
in the aqueous surfactant solution of identical
temperature under continuous stirring by high
shear device. This pre-emulsion is homogenized
using a piston-gap homogenizer and the produced
hot oil-in-water nanoemulsion is cooled down to
room temperature. The lipid recrystallizes and
leads to the formation of SLNs.[33-38]
Advantages
• Preparation without the use of organic solvent
• Feasibility of large-scale production
• High-temperature results in lower particle size
due to the decreased viscosity of the inner
phase
• Suitable for drugs showing some temperature
sensitivitybecausetheexposuretoanincreased
temperature is relatively short.
Disadvantages
• Poor technique for hydrophilic drugs
• Drug and carrier degradation is more at high
temperature
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• Due to small particle size and presence of
emulsifier, lipid crystallization may be highly
retarded and the sample remains as super-
cooled melt for several months
• Burst release of drugs from SLNs because
during heating the drug partitions into
aqueous phase and when cooled, most of
drug particles remained at the outer layer of
the SLNs
• Increasing the homogenization pressure or the
number of cycles often results in an increase
of the particle size due to particle coalescence
which occurs as a result of the high kinetic
energy of the particles.
Cold homogenization technique
In comparison to above, the cold homogenization
technique is carried out with the solid lipid and
represents, therefore, a high-pressure milling
of a suspension. The drug-containing lipid
melt is cooled, the solid lipid ground to lipid
microparticles (approximately 50–100 mm), and
these lipid microparticles are dispersed in a cold
surfactant solution yielding a pre-suspension.
Then, this pre-suspension is homogenized at or
below room temperature; the cavitation forces are
strong enough to break the lipid microparticles
directly to SLNs.[39,40]
Advantages
• Avoids temperature-induced drug degradation
and complexity of the crystallization step
• Minimizes the melting of lipid and therefore
minimizes the loss of hydrophilic drug to
aqueous phase
· Water from aqueous phase can be replaced
with other media (e.g., oil or PEG 600) with
low solubility for the drug
• Suitable for highly temperature-sensitive
compounds.
Disadvantages
• In comparison to hot homogenization, particle
size and polydispersity index are more
• Minimizes the thermal exposure of drug but
does not avoid it completely
• HPH increases the temperature of the sample
(10–20°C for each cycle.
SOLVENT EMULSIFICATION-
EVAPORATION TECHNIQUE
The solvent emulsification-evaporation technique
is a widespread procedure, being first used for
SLN preparation (precipitation in o/w emulsion)
by Sjöström and Bergenståhl.[41]
Lipid and drug
are dissolved in a water-immiscible organic
solvent by ultrasound and emulsified in an aqueous
phase containing surfactant/emulsifier using
magnetic stirrer (1000 rpm). The organic solvent
was evaporated by mechanical stirring at room
temperature and reduced pressure (e.g.,
rotary
evaporator) leaving lipid precipitates of SLNs.[42-44]
Advantages
• Very small particle size
• Suitable for the incorporation of highly
thermolabile drugs
• Avoids temperature-induced drug degradation.
Disadvantages
• Toxicity of solvent in the final product
• Extra step of filtration and evaporation.
Double emulsion technique
This method is based on the solvent emulsification-
evaporation technique in which the drug is
encapsulated with a stabilizer to prevent drug
partitioning to external water phase during
solvent evaporation in the external water phase
of w/o/w double emulsion. Primary emulsion
was formed by dissolving the hydrophilic drug
in aqueous solution, followed by emulsification
in melted lipid-containing surfactant/stabilizer.
The primary emulsion then dispersed in aqueous
phase containing hydrophilic emulsifier forming
the double emulsion.[45]
Solvent injection/solvent displacement
technique
It is a novel approach based on lipid precipitation
from the dissolved lipid in solution. The solid
lipid was dissolved in water-miscible solvent
forming the organic phase. This organic phase
was rapidly injected through an injection needle
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into an aqueous phase (with or without surfactant)
with continuous stirring. The resulted dispersion
was then filtered with a filter paper to remove any
excess lipid. The presence of emulsifier within the
aqueous phase helps to produce lipid droplets at
the site of injection and stabilize SLN until solvent
diffusion was complete by reducing the surface
tension between water and solvent.[46,47]
Advantages
• Use of pharmacologically acceptable organic
solvent
• Easy handling
•· Fast production process
• No use of technically sophisticated equipment
• Suitable for thermolabile drugs
• Small and uniform particle size distribution
• Avoidance of any thermal stress
• Avoids temperature-induced drug degradation.
Disadvantages
• Extra step of filtration
• Toxicity of solvent in final product.
Influence of ingredient composition on
product quality
Influence of the lipid
Using the hot homogenization, it has been found
that the average particle size of SLN dispersions is
increasing with higher melting lipids.[48]
However,
othercriticalparametersfornanoparticleformation
will be different for different lipids. Examples
include the velocity of lipid crystallization, the
lipid hydrophilicity (influence on self-emulsifying
properties,[49]
andtheshapeofthelipidcrystals(and
therefore the surface area). It is also noteworthy
that most of the lipids used represent a mixture
of several chemical compounds. The composition
might, therefore, vary from different suppliers
and might even vary for different batches from
the same supplier. However, small differences
in the lipid composition (e.g., impurities) might
have a considerable impact on the quality of SLN
dispersion (e.g., by changing the zeta potential and
retarding crystallization processes). For example,
lipid nanodispersions made with cetyl palmitate
from different suppliers had different particle
sizes and storage stabilities.
Influence of the emulsifier
The choice of the emulsifiers and their
concentration is of great impact on the quality of
the SLN dispersion.[29]
High concentrations of the
emulsifier reduce the surface tension and facilitate
the particle partition during homogenization.
The decrease in particle size is connected with a
tremendous increase in surface area. The increase
of the surface area during HPH occurs very rapidly.
Therefore, kinetic aspects have to be considered.
The process of a primary coverage of the new
surfaces competes with the agglomeration of
uncovered lipid surfaces. The primary dispersion
must contain excessive emulsifier molecules,
which should rapidly cover the new surfaces.
Different emulsifier compositions might require
differenthomogenizationparameters.Forexample,
the maximal degree of dispersing was obtained
with 500 bar and three cycles for poloxamer
188 stabilized systems.[50]
Homogenization with
pressures of 1000 or 1500 bar did not result in
further reduction of the particle size. In contrast,
pressures 1500 bar proved to be the best for
lecithin (lipoid 75)-stabilized systems. A possible
explanation for observation is the different
velocity of the coverage of the new lipid surfaces.
The particle size of the SLN dispersion produced
with the ionic surfactants was considerably smaller
compared to the non-ionic formulation.
Secondary production steps
Lyophilization
Lyophilization or freeze-drying is one of the
most significant secondary production steps
in nanoparticles preparation, which enhances
the physical and chemical stability of the
formulation obtained.[51]
Lyophilization aids to
increase the long-term stability for a nanoparticle
preparation with hydrolyzable drugs. When the
nanoparticulate systems are lyophilized into solid
preparation, it prevents Ostwald ripening as well
as hydrolytic degradation, thereby increasing the
stability. After lyophilization, NP can be more
easily incorporated into different dosage forms
such as tablets, capsules, parental dispersions,
and pellets. In lyophilization, the NP dispersion
is freezed which is then subjected to evaporation
under vacuum. Cryoprotectants such as sorbitol,
mannitol, glucose, and trehalose are added to
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the dispersion to prevent or minimize particle
aggregation and to redisperse the lyophilizates in
a more efficient way.
Spray drying
Spray drying is a less frequently used method
for transforming aqueous NP dispersion into a
dry product. Spray dryers make use of hot gases
and atomizers/nozzles to disperse effectively the
NP dispersion and, therefore, sometimes result
in aggregation and partial melting of NP. In case
of solid lipid NP, melting can be minimized by
incorporating ethanol in dispersion medium.[52]
Sterilization
Sterilization is another secondary production
step which is highly desirable for NP meant for
parenteral administration. Aseptic production
of NP, filtration, gamma irradiation, and heating
are the general methods used for sterilizing
nanoparticulate systems.[53]
In the case of heat-
resistant drugs and nanoparticle material,
autoclaving is a good method of choice. It was
also found that sterilizing of nanoparticulate
systems by this method could slightly increase
the particle size. Sterilization by filtration requires
high pressure and should not cause any change in
the nanoparticulate system with respect to stability
and drug release characteristics. In the case of
gamma irradiation, free radicals are obtained
and may undergo secondary reactions leading to
chemical modifications. High molecular mobility
and presence of oxygen enhance degradation
reactions induced by gamma radiations.[54]
PROBLEMS ASSOCIATED WITH
PREPARATION METHODS
High pressure-induced drug degradation
This problem is associated with the HPH
technique. The molecular weight of polymers
and the molecular structure are responsible for
the drug degradation. Formation of free radical
is responsible for the decrease in the molecular
weight of the polymers due to shear stress.
Almeida et al. (1997) reported that HPH -induced
drug degradation will not be a serious problem for
the majority of the drugs.[55]
Lipid modifications/polymorphism
The crystallized lipid may be present in several
modificationsofthecrystallattice.Lipidmolecules
have a higher mobility in thermodynamically
unstable configurations with lower density and,
ultimately, a higher capability to incorporate
guest molecules (e.g.,
drugs). During storage,
rearrangement of the crystal lattice might occur in
favor of thermodynamically stable configurations,
and this is often connected with the expulsion
of the drug molecules (Muller et al., 2000).
Thermodynamic stability and lipid packing
density increase with crystal order (supercooled
melt α-modification β’- modification
β-modification), on the contrary to the
crystallization kinetics.[56]
Particle shape
The shape of lipid nanoparticles (platelet form)
may significantly differ from a nanoemulsion
(sphere). Lipid nanoparticles have tendency to
crystallize in the platelet form; which are having
larger surface areas as compared to spheres
and require higher amounts of surfactants for
stabilization. As a result, much higher amount of
drug will be localized directly on the surface of
SLNs, which is in divergence with the general
aim of the SLN systems (drug protection and
controlled release due to the incorporation of the
drug in the solid lipid).[48,57]
Characterization of SLNs
An adequate characterization of the SLNs is
necessary for the control of the quality of the
product. Several parameters have to be considered
which have a direct impact on the stability and
release kinetics.
Entrapment efficiency and drug loading
Entrapment efficiency describes the efficiency
of the preparation method to incorporate drug
into the carrier system. A very important point to
judge the suitability of a drug carrier system is its
loading capacity. The loading capacity is generally
expressed in percentage related to the lipid phase
(matrix lipid: Drug). In addition, the amount of
drug entrapped also determines the performance
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of the drug delivery system since it influences the
rate and extent of drug release from the system.
Both drug loading and entrapment efficiency
depend on the physicochemical properties and the
interactions between the drug, carrier matrix, and
the surrounding medium.[30,58]
EE (%) = Ws/WTotal ×100 DL (%)
= Ws/WLipid ×100
Where, Ws - amount of drug loaded in the
SLNs; Wtotal - total drug amount in AD-SLNs
dispersion; Wlipid - weight of the vehicle.
Particle size and distribution
A particle size and distribution analysis is a
measurement designed to determine and report
information about the size and range of a set of
particles representative of a material. Particle
size and distribution analysis of a sample can be
performed using a variety of techniques such as
photon correlation spectroscopy, laser diffraction,
and aerodynamic technique.
Surface charge
The surface charge of a dispersed system is best
described by measuring the zeta (ζ) potential of
the system. This parameter is a useful predictor
of the storage stability of colloidal dispersions.
A minimum ζ potential of ± 30 mV is considered
the benchmark to obtain a physically stable
system. Particle aggregation is less likely to occur
for charged particles (high zeta potential) due to
electric repulsion. Zeta potential helps in designing
particles with reduced reticuloendothelial uptake.
To divert SLNs away from the RES, the surface of
the particles should be hydrophilic and free from
charge.[59]
Particle morphology and ultrastructure
Particle size results are often validated by
transmission electron microscopy, which provides
direct information on SLN morphology and
ultrastructure. In this, an electron beam is focused
and directed through a sample by several magnetic
lenses, with part of the beam adsorbed or scattered
by the sample, while the remaining is transmitted.
The transmitted electron beam is magnified
and then projected onto a screen to generate an
image of the specimen. The fraction of electrons
transmitted depends on sample density and
thickness (typically 100 nm).[60-62]
SEM uses a focused electron beam to generate a
variety of signals (i.e., backscattered or secondary
electrons) at the surface of solid specimens.
The signals derived from electron-sample
interactions reveal information about the sample
including morphology, chemical composition, and
potentially crystalline structure.[63,64]
In vitro assessment of drug release
In vitro release studies are generally performed to
accomplish the objectives such as:
• Indirect measurement of drug availability,
especially in preliminary stages of product
development.
• Quality control to support batch release and to
comply with specifications of batches proven
to be clinically and biologically effective.
• Assess formulation factors and manufacturing
methods that are likely to influence
bioavailability.
• Substantiation of label claim of the product.
• As a compendial requirement.[65]
In vitro release study tells about basic information
regarding the structure (e.g.,
porosity) and
behavior of the formulation at molecular level,
possible drug-excipient interactions, and about
the factors influencing the rate and mechanism
of drug release.[66]
Such information facilitates a
scientific and predictive approach to the design
and development of sustained delivery systems
with desirable properties. Various methods have
been reported to study the in vitro drug release,
and the most common technique is membrane
diffusion techniques.
CONCLUSIONS AND FUTURE
OUTLOOK
Low water solubility is widely recognized as the
main reason for the poor oral absorption of many
drugs. Several types of approaches have been
proposed to improve the aqueous solubility of
poorly water-soluble drugs. In particular, for BCS
Class II drugs, increasing their solubility and/or
dissolution rate would be a promising approach
to enhance the oral bioavailability. Conventional
solubilization approaches which include the
use of surfactants, complexes, salt formations,
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nanoparticles, solid dispersions, lipids, and
permeation enhancers are employed in enhancing
theoralabsorptionofdrugs.However,SLNisoneof
the most promising approaches for improving oral
delivery of BCS Class II drugs. Clear advantages
of SLN include the composition (physiological
compounds), the rapid and effective production
process including the possibility of large-scale
production, the avoidance of organic solvents, and
the possibility to produce high concentrated lipid
suspensions. Disadvantages include low drug-
loading capacities, the presence of alternative
colloidal structures, and the complexity of the
physical state of the lipid which cause stability
problems during storage or administration of SLN.
Further work needs to be done to understand
the interaction of SLN with their biological
surrounding (adsorption/desorption processes,
enzymatic degradation, agglomeration, and
interaction with endogen). The SLNs as drug
nanocarriers have the potential to achieve the
broad objectives for treating various diseases.
A wider collection of the lipid materials may be
illustrated for SLNs in the future. The lipids from
natural sources can be a major origin of the SLN
lipid matrix. More patented dosage forms of SLNs
can be expected in the near future.
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