This document presents information on parenteral depot systems for long acting drug formulations. It discusses various approaches for controlled drug release including the use of viscous vehicles, polymeric microspheres, and drug derivatives. Common polymers used in depots are described as well as desirable characteristics. The main types of depot formulations are discussed - dissolution controlled, adsorption, encapsulation, and esterification. Examples of specific long acting preparations are provided for antibiotics, insulin, vitamin B12, and contraceptives. Evaluation methods and the development of depots are outlined.
Video Lecture is available at https://www.youtube.com/watch?v=DXu_CLgB4q0
Introduction, terminology/definitions and rationale, advantages, disadvantages, selection of drug candidates. Approaches to design-controlled release formulations based on diffusion, dissolution and ion exchange principles. Physicochemical and
biological properties of drugs relevant to controlled release formulations.
Video Lecture is available at https://www.youtube.com/watch?v=DXu_CLgB4q0
Introduction, terminology/definitions and rationale, advantages, disadvantages, selection of drug candidates. Approaches to design-controlled release formulations based on diffusion, dissolution and ion exchange principles. Physicochemical and
biological properties of drugs relevant to controlled release formulations.
Description about a type of activation modulated drug delivery system, which a type of control drug delivery system.
Also, give a detailed description about each subclassification.
CrDDS is one which delivers the drug at a predetermined rate, for locally or systematically, for a prolong period of time.
introduction
mechanisms of protein drug binding
binding of drugs
binding of drugs to blood components
determination of protein drug binding
factors affecting
significance
Description about a type of activation modulated drug delivery system, which a type of control drug delivery system.
Also, give a detailed description about each subclassification.
CrDDS is one which delivers the drug at a predetermined rate, for locally or systematically, for a prolong period of time.
introduction
mechanisms of protein drug binding
binding of drugs
binding of drugs to blood components
determination of protein drug binding
factors affecting
significance
ABSTRACT
The parenteral administration route is the most effective and common form of delivery for active drug substances with poor bioavailability and the drugs with a narrow therapeutic index. Drug delivery technology that can reduce the total number of injection throughout the drug therapy period will be truly advantageous not only in terms of compliance, but also to improve the quality of the therapy and also may reduce the dosage frequency. Such reduction in frequency of drug dosing is achieved by the use of specific formulation technologies that guarantee the release of the active drug substance in a slow and predictable manner. The development of new injectable drug delivery system has received considerable attention over the past few years. A number of technological advances have been made in the area of parenteral drug delivery leading to the development of sophisticated systems that allow drug targeting and the sustained or controlled release of parenteral medicines.
Vesicles are colloidal particles in which a concentric bilayer made-up of amphiphilic molecules surrounds an aqueous compartment Useful vehicle for drug delivery of both hydrophobic drugs and hydrophilic drugs, which are encapsulated in the interior aqueous compartment.
Nanoparticles, types, preparation and evaluation ppt.pptxmanjureddy62
This ppt consists of information related to nanoparticles, their types and preparation and evaluation. it also consists of questions from the previous years exams conducted by RGUHS (Karnataka) university. Targeted drug delivery.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. Presented by-
Miss Shraddha M.
Kumbhar
M. Pharm (Pharmaceutics)
Satara college of
Under the guidance of -
Dr. Ajit S. Kulkarni
Vice-Principal
Satara college of Pharmacy,
Satara
A
Colloquium
on
1
2. Introduction
•Parenteral route: most effective
•To achieve constant drug level in the systemic
circulation, two strategies can be employed:
1)To control the rate of absorption of a drug.
2)To control the rate of excretion i. e. by modifying
physiology of body.
Depot: Long acting parenteral drug formulation is
designed, ideally to provide slow, constant,
sustained, prolonged action.
The release can either be continuous or pulsatile
depending on the structure of the device and the
polymer characteristics.
2
3. Parenteral depot system:
Properties:
• Safe from accidental release
• Simple to administer and remove
• Inert and Biocompatible
• Comfortable for the patient
• Capable of achieving high drug loading
• Easy to fabricate and sterilize
• Free of leachable impurities
3
4. Approaches used…
• Use of viscous, water miscible vehicles – aq.
Solution of gelatin
• Use of water immiscible vehicles – vegetable oils +
aluminium monosterate
• Formation of thixotropic suspension
• Preparation of water insoluble drug derivatives –
salts, complexes and esters
•Dispersion in polymeric microspheres and
microcapsules like- lactide-glycolide
homopolymers/ co-polymers.
• Co-administration of vasoconstrictors
4
5. Polymers used……
Generally, Biodegradable polymers are used as it
get degraded in the body.
•Natural- albumin, starch, dextran, gelatin,
fibrinogen, hemoglobin.
•Synthetic- poly ethyl-polyalkyl cynoacrylates, poly
amides, poly acryl amides, poly amino acid, poly
urethane.
5
6. Desirable characteristics of an ideal
Parenteral drug carrier
• Versatile
• High capacity to carry a sufficient quantity of
drug
• Uniform distribution
• Restricting drug activity at the target site over a
prolonged period.
• Protecting drug from inactivation by plasma
enzymes.
• Biocompatible and minimally antigenic.
• Undergoing biologic degradation with minimal 6
7. TYPES OF DEPOT
FORMULATION
1. Dissolution controlled depot formulation
2. Adsorption type depot formulation
3. Encapsulation type depot formulation
4. Esterification type depot formulation
7
8. Dissolution controlled depots
RDS of drug absorption is dissolution of drug.
• Approaches :
Formation of salt or complexes with low aqueous
solubility.
Example:
penicillin G procaine (Cs = 4 mg/ml) and
penicillin G benzathine (Cs = 0.2 mg/ml).
Suspension of Macrocrystals:
to control the rate of drug dissolution.
Example: aqueous suspension of testosterone
isobutyrate for intramuscular administration. 8
9. Adsorption type depots
This depot preparation is formed by the binding of
drug molecules to adsorbents.
Example: vaccine preparations in which the
antigens are bound to highly dispersed aluminum
hydroxide gel to sustain their release and hence
prolong the duration of stimulation of antibody
formation.
9
10. Encapsulation-type depots
prepared by encapsulating drug solids .
-The release is controlled by the rate of
permeation across the permeation barrier and the
rate of biodegradation.
Biodegradable or bio absorbable macromolecules
are used, e. g. gelatin, dextran, poly lactic acid,
lactide-glycolide copolymers, phospholipids, and
long-chain fatty acids and glycerides.
Example:
naltrexone pamoate –
releasing biodegradable microcapsule, 10
11. Esterification-type depots
produced by esterifying a drug to form a
bioconvertible prodrug-type ester.
The rate of drug absorption is controlled by
the interfacial partitioning of drug esters from
the reservoir to the tissue fluid and the rate of
bioconversion.
Example: fluphenazine enanthate,
nandrolone decanoate in oleaginous solution.
11
12. Parenteral Controlled Drug
Delivery System
A. Inject able drug delivery
B. Implantable drug delivery
system
C. Infusion devices
D. Recent advances
12
13. Injectable Drug Delivery
1. Thermoplastic pastes
2. In situ cross linked systems
3. In situ polymer precipitation
4. Thermally induced gelling
system
5. In situ solidifying organogels.
13
14. Thermoplastic pastes
•In this semisolid polymers are injected as a melt
and form a depot upon cooling to body temperature.
•having a low melting point (25-65˚C) intrinsic
viscosity (0.05-0.8 dl/g).
•Drugs are incorporated into the molten polymer by
mixing without the application of solvents.
•Polymers: D, L-lactide, glycolide, E-caprolactone,
dioxanone orthoesters etc.
•polycaprolactone (PCL) requires injection
temperature at least 60˚C i.e. painful injections and
necrosis at the injection site,POE have good
biocompatibility, relatively low softening14
15. In situ polymer precipitation
water-insoluble,
biodegradable polymer
+ biocompatible organic
solvent + drug
solution
or
suspensio
n after
mixing.
When this
formulation is
injected into
the body, the
water miscible
organic solvent
dissipates and
water
penetrates into
the organic
phase.
This leads to
phase
separation
and
precipitation
of the
polymer
forming the
depot at the
site of
injection
15
16. Thermally induced gelling system
•Environmental temperature causes change in
solubility of thermo sensitive polymers.
•Example:
Poly (NIPAAM) exhibit sharp lower critical solution
temperature, LCST at about 32˚C, poly NIPAAM
based gels with salt and surfactant shows release
over 10-20d.
16
18. SLN
•SLN are submicron colloidal particles composed of
a biocompatible/biodegradable lipid matrix that is
solid at body temperature.
•size range : 100-400 nm.
•Generally physiological lipid dispersed in water or in
aqueous surfactant solution. SLNs combine
advantages of polymeric nanoparticles, fat
emulsions and liposomes.
Advantages:
•Particulate nature
•encapsulate hydrophilic and hydrophobic drugs
•Ability to sustain the release, to prevent chemical,
photochemical, or oxidative degradation of drug 18
19. Nanodispersions
Nanoemulsions / miniemulsions / submicron emulsions:
These are transparent or translucent oil-in-water (o/w) or
water-in-oil droplets with a mean droplet diameter in the
range between 100 and 500 nm. great stability due to their
small droplet size.
Nanosuspensions:
Nanosuspensions of drugs are submicron colloidal dispersions
of drug particles which are stabilized by
surfactants. Nanocrystals are crystals of poorly water soluble
drug in nanosize.
Advantages: Used to formulate drugs that are insoluble in both
water and oil, have higher loading (upto 90% of crystalline
particle is drug).
Used when drug have high melting point.
19
20. Suspensions
•Drug release dependent upon both the intrinsic
aqueous solubility of the drug and the dissolution
of the drug particles.
•Example: Abbott laboratories developed aqueous
thixotropic suspension of penicillin procaine (40-
70%w/w), such as Duracillin (Lilly), Crystacillin
(Squibb) which on intramuscular injection
produces therapeutic blood level of penicillin in
both animal and human for 162hr
20
21. Niosomes
These are nonionic surfactant vesicles obtained on
hydration, with or without incorporation of cholesterol
or other lipids.
•These are bilayered structure which can entrap both
hydrophilic and lipophilic drugs.
•Drug is incorporated into by….
Ether injection-Doxorubicin,
Hand shaking- Methotrexate,
Sonication- Vasopressin
21
22. Liposomes
•Liposomes are formed by the self-assembly of
phospholipids molecules in an aqueous
environment.
•Drug incorporated in alternating aqueous and lipid
compartments ,
•Sustained release
•lasting over several days to weeks.
•Example: myelopoietin (Leridistim)
22
23. Microspheres
•Contains dispersed molecules either in solution or in
crystalline form, biodegradable polymers are used.
Magnetic microspheres increases target site
specificity & non-toxic and non-reactive with blood
components.
Examples:
Minocycline Arestin® Orapharma,
Bromocriptine Parlodel LAR ™ Novartis
23
24. EMULSOMES
•Emulosomes are lipid based drug delivery
systems, which are poorly water soluble.
• Emulosome particles are basically consisting of
microscopic lipid assembly with a polar core.
•Prepared by- melt expression/ emulsion solvent
diffusive extraction.
•Used as adjuvants for vaccines, as carrier
container for targeted drug delivery to liver, brain
and RES rich organs
24
25. Resealed Erythrocytes
•Here erythrocytes lose their haemoglobin content
when they are processed by various methods i.e.
osmolysis, electrical breakdown/electro-encapsulation,
endocytosis etc.
•Hb loss provides intracellular space for drug
incorporation. Erythrocytes membrane can be
resealed by restoring tonicity of the media and
incubating them at 37°C.
•t1/2= 60-120 days.
•biodegradable, biocompatible, and non-immunogenic.
25
26. Cyclodextrins
• Cyclodextrins are water soluble cyclic
carbohydrate compounds with
hydrophobic cavity.
• forms inclusion complexes with
hydrophobic molecules
• Example:
• Sulphobutyl β- cyclodextrin
Nimodipine aq. suspension –the
relative solubility of the drug is
increased with no change in drug
AUC.
26
27. AQUASOMES
• Aquasomes are 3-layered self assembling
composition.
• solid or glassy particles dispersed in an aq.
Environment & MOA is controlled by their
surface chemistry.
• For gene therapy, a 5- layered composition of
Aquasome comprised of the ceramic mono
crystalline core, the polyhydroxyl oligomeric film
coating, the noncovalently bound layer of
therapeutic gene segment, an additional
conserve viral membrane proteins have been
proposed for gene therapy
27
28. Dendrimers
• Dendrimers are highly branched 3-D-
macromolecules with highly controlled structures
with all bounds emanating from a central core.
• Methods-
Divergent method-
one branching unit after another is successfully
attached to the core molecule.
Convergent method-
where the skeleton in built stepwise starting from
the end group towards the inside and finally
treated with a core molecule to produce the
Dendrimer. 28
29. Implantable drug delivery system
• Implant systems are indicated in case of chronic
therapy, such as hormone replacement therapy.
Parenteral implants can be highly viscous liquids
or semisolid formulations.
• Polymers used – polysaccharides, polylactic
acid coglycolic acid (no need for surgical
removal of the implant after treatment) and non
degradable methacrylates.
• Types:
1. Solid implants
2. In situ forming implants 29
30. Infusion devices
• Osmotic pumps(alzet):
After implantation, water from the surrounding tissue
fluids is imbibed through the semi permeable
membrane.
Drug release osmotic pressure difference.
Ionized drugs macromolecules, steroids, and
peptides (insulin) can be delivered by such a device.30
31. • Vapour pressure powered pumps
(Infusaid):
After implantation, the volatile liquid vaporizes at the
body temperature and creates a vapor pressure.
Example:
Insulin for diabetics and morphine for terminally ill
cancer.
shows back flow of infusate.
• Battery powered pumps:
Types:
1. Peristaltic pump
2. Reciprocating pump,
both with electronic controls.
Do not show back flow of the infusate. 31
33. Development of depots:
• Long acting antibiotic preparations:
aqueous solubility of penicillin is reduced by
converting to penicillin G procaine (aq. Solubility
4mg/ml) e.g. Duracillin (Lilly)
• Long acting insulin preparations:
Plasma t1/2 of insulin = 40 min
insulin-protamine complex has isoelectric point at
pH 7.3 and therefore it is insoluble in body fluid
which shows sustained release upto 24 hrs,
stability issues arises but solved by adding zinc
chloride.
33
34. Development of depots:
• Long acting vit.B12 preparations:
Vit.B12–zinc-tannate complex is suspended in
sesame oil gelled with aluminium-monostearate
having significant prolonged effect.
• Long acting adrenocorticotropic hormone
preparations:
when given parenterally ACTH gets disappeared
cause of plasma t1/2 15 min. addition of partially
hydrolyzed gelatin solution into injectable ACTH
solution shows prolonged release. Gelatin inhibits
protein binding of ACTH and enhances response. 34
35. Development of depots:
• Antipsychotic depots:
Example:
Piportil-Pipothiazinepalmitate up to 200 milligrams 1
injection every 4 weeks
• Long acting anti-narcotic preparations:
Gelled oleaginous suspension of narcotic antagonist
–salt complex shows sustained release for 72 hrs
• Long acting contraceptive preparations:
Norethindrone in a biodegradable polymer beads.
Norgestrel 17β-fatty acid esters in oleaginous
solution.
35
36. Conclusion
Parenteral controlled drug delivery system is
designed to achieve a desired
pharmacological response in a sustained
manner at a selected site without
undesirable interactions at the other sites.
Extended release parenteral products are
complex dosage forms, requiring careful
development of test methods and
acceptance criteria for the specifications
36
37. References
• Bari H.(July-Aug2010)A Prolonged Release Parenteral
Drug Delivery System- An Overview, ISSN(vol 3,p.1-11)
• Chien Y. W., Novel Drug Delivery Systems; Drugs and
Pharmaceutical Sciences(2nded, vol-50) Parenteral Drug
Delivery (pp-381-528),New York: Marcel Dekker.
• David A. S. & Adams C.(2001) Depot antipsychotic
medication in treatment of patients with schizophrenia,
Health Technology Assessment (vol 5, 34), Basingstoke:
Queen’s printer and controller of HMSO
• Gothoskar A. V. (March 2004),Resealed erythrocytes: A
review, Pharmaceutical technology (pp.140-158)
• Kempe S. & Mader K.(July 2012),In-situ forming
implants-an attractive formulation principle for parenteral
depot formulation, Journal of Controlled Release
(pp.668-679)
37
38. References
• Lachman L. & Libberman H. & Kanig J.(2007) Sterile
products(pp.653-654),Bombay: Varghese Publishing
House.
• M. Kalyani & P.Surendra & V. Sirisha(2013).Parenteral
Controlled Drug Delivery System, International Journal
Of Research In Pharmaceutics & Nanosciences (pp.572-
580)
• Malik K. & Sigh I. & Nagpal M. & Arrora S.(2010),
Atrigel: A potential Parenteral control Drug delivery
system, pelagia research lab der pharmacia sinica
(pp.74-81)
• Mischel N. & Cox L.(2012),Allergen Immunotherapy
Extract Preparation Manual, AAAAI Practice
Management Resource Guide(pp.1-39) 38
39. References
• Vyas S. P. & Khar R. K.(2006), Targeted and
Controlled Drug Delivery Novel Carrier Systems(pp.3-
38;173-279; 387-457) New Delhi: CBS Publishers and
Distributors.
• Wheeler A. M. & Newland B. Advantages of L-tyrosine
as a depot adjuvant for formulation of therapeutic
allergy vaccines; Allergy therapeutics: transforming
allergy treatment
• www.pharmatutor.org/articles/aquasomes-potential-
approach-novel -drug-delivery
• www.pharmatutor.org/articles/information-and-article-
on-erythrocytes-as-a-drug carrier.
• www.pharmatutor.org/articles/review-parenteral-
controlled-drug -delivery-system
39