This document presents a study on the development of rifampicin (RIF) loaded nanostructured lipid carriers (NLCs) for pulmonary delivery to treat tuberculosis. Key points:
1. RIF-loaded NLCs were developed and characterized to target infected alveolar macrophages. A ligand-conjugated formulation was also designed for active targeting.
2. Analytical methods for RIF were standardized and validated. Excipients were screened to optimize the lipid composition. A 3^3 Box-Behnken design was used to optimize formulation variables.
3. The developed NLCs showed high entrapment efficiency and appropriate size for lung delivery. A spray drying technique was used to
Colloidal particles ranging in size between 10 & 1000 nm are known as nanoparticles.
SLNs are new generation of submicron sized lipid emulsion where the liquid lipid(oil) has been substituted by a solid lipid.
Example: Capture - Dior
Colloidal particles ranging in size between 10 & 1000 nm are known as nanoparticles.
SLNs are new generation of submicron sized lipid emulsion where the liquid lipid(oil) has been substituted by a solid lipid.
Example: Capture - Dior
Particles in the Biotech Product Life Cycle: Analysis, Identification and Con...SGS
This presentation looks at the different technologies available for detection of particles generated during the drug development lifecycle and their control using a formulation approach for particles generated as a result of agitation and freeze/thaw, events commonly observed during sample shipment and temperature excursions.
Particles in the Biotech Product Life Cycle: Analysis, Identification and Con...SGS
This presentation looks at the different technologies available for detection of particles generated during the drug development lifecycle and their control using a formulation approach for particles generated as a result of agitation and freeze/thaw, events commonly observed during sample shipment and temperature excursions.
High Performance Liquid Chromatographic Technique and Validation for Determin...ijtsrd
Favipiravir is an antiviral that is active against many RNA viruses, and also used in COVID 19. A simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir. It was resolved on the C18 column using the mobile phase blend of methanol acetonitrile ortho phosphoric acid in an isocratic mode, flow rate of 1.0 mL min with a proportion of 40 30 30 ,v v v. The detector wavelength was set at 322 nm. Reverse phase HPLC method, using UV detector is developed for the estimation of Favipiravir API. Used Liquid chromatographic system from Shimadzu comprising of Auto sampler, quaternary gradient pump for constant flow and constant pressure delivery and UV Visible detector connected to software Lab solutions for controlling the instrumentation as well as processing the generated data. A mixture of Methanol Acetonitrile Ortho phosphoric acid in the ratio 40 30 30 v v v was used in RP HPLC as diluent and as a mobile phase. Ms. Pritee R. Atkar | Dr. Mirza Shaihed Baig "High Performance Liquid Chromatographic Technique and Validation for Determination of Favipiravir in Bulk & Tablet Formulation" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-7 , December 2022, URL: https://www.ijtsrd.com/papers/ijtsrd52424.pdf Paper URL: https://www.ijtsrd.com/pharmacy/other/52424/high-performance-liquid-chromatographic-technique-and-validation-for-determination-of-favipiravir-in-bulk-and-tablet-formulation/ms-pritee-r-atkar
Bioethanol production from cheese whey.pptxAsmamawTesfaw1
It deals about production of bioethanol from cheese whey which is not sterilized and other characters of the ethanol producing yeasts were also covered
Bioethanol production from cheese whey.pptxAsmamawTesfaw1
It deals about production of bioethanol from cheese whey which is not sterilized and other characters of the ethanol producing yeasts were also covered
Development and Validation of Reversed-phase High-performance Liquid Chromato...BRNSS Publication Hub
A new, reliable, and sensitive reversed-phase high-performance liquid chromatography method has been developed and validated for simultaneous assay of benzoyl peroxide (BPO) and resveratrol. An isocratic separation of BPO and resveratrol was achieved on C18, 250 mm × 4.6 mm I.d., 5 μm particle size columns with a flow rate of 1.2 ml/min and using a UV detector to monitor the elute at 245 nm. The mobile phase consisted of an ammonium acetate (pH 4) and ethanol. Response was a linear function of drug concentration in the range of 10–100 mg/mL range with an R2 of 0.993 for BPO and 10–100 μg/mL range with an R2 of 0.995 for resveratrol, accuracy with percent relative standard deviation of 100.65 ± 0.23 (benzoic peroxide) and 100.48 ± 0.45 (resveratrol) and with a limit of detection and quantification for BPO and resveratrol, respectively. The result of analysis has been validated statistically and by recovery study. The accuracy ranged between 99.65 and 101.91%. The method was found to be precise, reproducible, and rapid.
Validation of anti niv igm capture elisa version#1krishgen
NiV is a negative-sense, non-segmented RNA virus that was first isolated from cerebrospinal fluid of human patients and classified in the family Paramyxoviridae under the new genus
Henipavirus. Its genome encodes six structural proteins: the nucleocapsid (N) protein,
phosphoprotein (P), matrix (M) protein, fusion (F) protein, glycoprotein (G), and large (L)
protein.
Nipah virus glycoprotein G has a globular head domain formed of a six-bladed beta sheet propeller, connected via a flexible stalk domain to a transmembrane anchor. The G binds to the cellular receptors ephrin B2 are ephrin B3, mediating viral attachment. Following attachment Nipah Virus glycoprotein G undergoes a conformational change that leads to triggering of glycoprotein F which leads to membrane fusion (Biering et al, 2012).
The Nipah virus glycoprotein G is a recombinant protein expressed in mammalian HEK293 cells. It is presented as a fusion protein with a mouse Fc tag linked to the C-terminus of glycoprotein G, amino acids 71-602.
We established preliminary specifications defining acceptable ranges for the parameters indicated herein below for our Anti Nipah Virus IgM Capture ELISA kit. These parameters were tracked day-to-day, run-to-run, and operator-to-operator, over a schedule defined inhouse.
Recommended assay characteristics included absorbance of a zero concentration standard; factors which describe the calibration for each standard and statistical description of the calibration curve such as coefficient of correlation, slope and/or intercept; and recovery of results on control samples. It is important to be able to relate the specifications for a parameter to expected reliability of the result. Our in-house standard defined was r=0.990.
The mixing process in the production of paracetamol suspension and its stabilityAI Publications
The mixing process is a common and important process in the chemical, food and pharmaceutical industries with the objective of producing suspensions and emulsions and increasing the process rate of mass and heat transfer. In this paper, the mixing process was studied during the production of paracetamol syrup in a new formula with a concentration of (10 g / 100 ml). For this purpose, a four-blade mixer was designed and the factors affecting the mixing process and the stability of the final product were studied including the mixing time and speed of rotation.
Similar to Nanostructured Lipid Carrier based Dry Powder Inhaler (DPI) of Anti TB drug. (20)
This presentation has been made for educational purpose. The presentation covers microscopic characteristics of kurchi bark. The transverse section, powder microscopy, micro-chemical tests and chemical tests of kurchi bark are discussed in presentation . The presentation is useful for preparation of competitive examinations like GPAT.
The presentation covers microscopic characteristics of Rauwolfia. The transverse section, powder microscopy, micro-chemical tests and chemical tests of Rauwolfia are discussed in video lecture. It is useful for preparation of competitive examinations like GPAT.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Nanostructured Lipid Carrier based Dry Powder Inhaler (DPI) of Anti TB drug.
1. DESIGN OF LIPID
PARTICULATE SYSTEM FOR
INFECTIOUS DISEASE
Presented by - Vipul A. Sansare.
Bombay College Of Pharmacy, Mumbai.
2. CONTENTS
1. Tuberculosis
2. Standardization and analytical method development
for Rifampicin (RIF)
3. Synthesis and characterization of ligand
4. Development and characterization of RIF loaded
nanostructured lipid carrier (NLCs)
5. Development and characterization of dried powder
for inhalation of RIF loaded NLCs
6. Summary and conclusion
7. References
8. Acknowledgements
7/18/2018
2
3. INTRODUCTION
7/18/2018
3
Tuberculosis :Mycobacterium tuberculosis
Oral/parenteral
administration
Nonspecific distribution in
human body
Dose related side effects
(hepatotoxicity, epigastric
pain)
Less amount of drug
accumulate in AM
high drug
concentration in
the lung
Target alveolar
macrophages
Noninvasive
Reduce dose
related side
effects
Survival of
TB bacteria
in AM
Entry of TB
bacteria in
AM
Inhibit
phagosome
lysosome
fusion
Inhibit
disruption
by
lysosomal
enzymes
Adapted in
environment
of AM
4. AIM AND OBJECTIVE
7/18/2018
4
Aim of the present study was to develop ligand conjugated RIF loaded
nanostructured lipid carrier (NLCs) based dry powder for inhalation and
their characterization.
1. Fabrication and characterization of RIF loaded NLCs for passive targeting to
infected alveolar macrophages.
2. Design and evaluation of ligand conjugated NLCs containing RIF for active
targeting to infected alveolar macrophages.
Fig. 1 Receptors on AM
8. 7/18/2018
8
• A 5 mmol of stearyamine was dissolved in 15ml
ethanol and heated up to 700C.
• 5 mmol of D-Mannose was added with stirring
• The solution was stirred for 15 min at 700C. After 15
min the solution was allowed to cooled down to
400C.
• The solution was diluted with 35ml hexane.
• The obtained crystals were washed with 30ml
hexane and ethanol and collected by filtration at
room temperature.
Stearylamine
D-Mannose N-Octadecylmannopyranosylamine
9. 7/18/2018
9
Fig. 3 IR spectrum of D-Mannose, Stearylamine and NODM
3398
2926
1638
1064
3331
2917
2849
1463
1606
2917
2850
3383
1465
1071
13. OPTIMIZATION OF RATIO OF SOLID LIPID TO LIQUID LIPID
7/18/2018
13
Ratio of stearic acid:
oleic acid
Presence of oil droplets on
filter paper
Result
5:5 Yes Not selected
6:4 Yes Not selected
7:3 Yes Not selected
8:2 No selected
9:1 No Not selected
Miscibility test
17. MODEL FOR PARTICLE SIZE 7/18/2018
17
Parameter Experimental value Required value
Model F-value 16.97 -
Probability ˃ F for model 0.0001 ˂ 0.05
Probability ˃ F for factor A 0.0001 ˂ 0.1
Probability ˃ F for factor B 0.7840 ˂ 0.1
Probability ˃ F for factor C 0.0001 ˂ 0.1
Probability ˃ F for factor AC 0.5969 ˂ 0.1
Predicted R-square 0.8106 -
Adjusted R-square 0.7134 -
Adequate Precision 15.14 ˃ 4
Particle size = +481.34 +
15.72A + 0.7750B - 16.40C +
2.12AC
Fig.6 3-D, contour and
perturbation plot
18. MODEL FOR ENTRAPMENT EFFICIENCY (%) 7/18/2018
18
Parameter Experimental value Required value
Model F-value 53.50 -
Probability ˃ F for model 0.0001 ˂ 0.05
Probability ˃ F for factor A 0.0001 ˂ 0.1
Probability ˃ F for factor B 0.0001 ˂ 0.1
Probability ˃ F for factor C 0.1079 ˂ 0.1
Probability ˃ F for factor AB 0.3481 ˂ 0.1
Probability ˃ F for factor AC 0.9559 ˂ 0.1
Probability ˃ F for factor BC 0.798 ˂ 0.1
Probability ˃ F for factor A2 0.134 ˂ 0.1
Probability ˃ F for factor B2 0.4991 ˂ 0.1
Probability ˃ F for factor C2 0.4362 ˂ 0.1
Predicted R-square 0.8406 -
Adjusted R-square 0.9672 -
Adequate Precision 28.104 ˃ 4
Entrapment efficiency = +55.10 + 6.91A +5.31B + 0.0325C + 0.57AB +
0.0325AC +0.15 BC -0.9363 A² - 0.3938B2 -0.4562C2
20. VALIDATION OF MODEL FOR PARTICLE SIZE
7/18/2018
20
Checkpoint
batch
Total lipid
(% w/v)
Lipid : drug
ratio
Surfactant
concentratio
n (% w/v)
Predicted
value (nm)
Observed
value (nm)
% Error
1 3 35 1.5 473.12 477.4 0.9046330
2 4 50 1.5 481.33 487.6 1.3026406
3 5 65 1.5 489.8 496.2 1.3066557
Fig.8 Validation of model for particle size
21. VALIDATION OF MODEL FOR ENTRAPMENT EFFICIENCY
7/18/2018
21
Checkpoint
batch
Total lipid
(% w/v)
Lipid : drug
ratio
Surfactant
concentration
(% w/v)
Predicted
value (%)
Observed
value (%)
% Error
1 3 35 1.5 48.69 50.19 2.98864316
2 4 50 1.5 54.958 55.16 0.3662074
3 5 65 1.5 61.384 62.23 1.35947292
Fig.9 Validation of model for entrapment efficiency
22. CHARACTERIZATION OF RIF NLCS
7/18/2018
22
Appearance: homogeneous and red in colour,
Particle Size and Polydispersity Index (PDI): using Zetasizer Nano ZS
(Malvern) 240.9 nm (PDI=0.135)
Zeta potential: - 43.3 mV
Entrapment efficiency: 52±0.88%.
Fig.10 Zeta potential of optimize formulation
24. 7/18/2018
24
Feed rate 1ml/min
Atomization pressure 2 bars
Inlet temperature 105-110 0C
Outlet temperature 50-60 0C
Vacuum 135-140 mm of Hg
Product temperature 40-500C
Spray drying of RIF NLCs
Spray drier: Labaultima
Carrier: Mannitol
Antiadherent: L-Leucine
Lipid: carrier ratio: (1:2)
Table: Operating conditions for spray drying
Aggregation
Exhalation
(nano size)
Drawbacks of NLCs for pulmonary delivery
Sedimentation
25. PARTICLE SIZE AND ASSAY
7/18/2018
25
Particle Size and Polydispersity Index (PDI): using Zetasizer Nano ZS
(Malvern) 409.5nm, (PDI= 0.324)
Assay: using UV spectroscopy from three different locations of container.
91 ± 2.6 %.
Fig.11 Particle size of redispered spray dried NLCs
26. SURFACE MORPHOLOGY
7/18/2018
26
Scanning Electron Microscopy (Philips XL 30)
Flow properties
Compressibility index: 16.66
Hausners ratio: 1.2
Angle of repose: 29.360
Fig.12 SEM images of RIF, spray dried RIF NLCs
28. 7/18/2018
28
Spray dried RIF NLCs
Total drug impinged (µg) 3000
Recovered dose (µg) 2746.063
Emitted dose(µg) 2667.15
FPD(µg) 1211.53
FPF (%) 44.1188
Dispersibility (%) 45.42414
MMAD (µm) 4.71
GSD 1.71
Fig.13 Comparative plot of % of RIF deposited on stages of ACI
29. IN–VITRO RIF RELEASE STUDY
7/18/2018
29
Apparatus Dissolution apparatus (Labindia)
Release medium Simulated lung fluid pH 7.4
Volume of release medium 150ml
Membrane
Dialysis membrane (13-14kD)
Temperature 37±0.50C
Stirring speed 50 rpm
Study duration 96 hours
Quantity of RIF Equivalent to 3mg of RIF (403.26mg)
Volume of aliquot 5ml
Time points
0,0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96
hours
0
10
20
30
40
50
60
70
80
90
0 20 40 60 80 100
%Cumulativerelease
Time (hours)
RIF NLCs
RIF
Fig.14 In-vitro release profile of RIF from NLCs
84.1±4.34% of RIF release
at the end of 96 hrs.
30. X-RAY DIFFRACTION
7/18/2018
30Fig.15 XRD diffractogram of mannitol, RIF, RIF
NLCs
2Ɵ values Intensity of peak for
RIF pure drug
Intensity of peak for
RIF NLCs with
conjugation
7 4376 1685
9.93 5939.7 No peak
11.13 13911.39 182
15.72 11176 No peak
19.94 13561.97 770
Bruker D8 Discover XRD analyzer
35. 7/18/2018
35
• RIF NLCs for active targeting to AM were prepared using
stearic acid, oleic acid and tween 20 using melt
homogenization ultrasonication method. RIF NLCs were
converted into dry powder by spray drying.
• Spray dried RIF NLCs showed good redispersibility,
morphology, and flow properties.
• In-vitro lung deposition study showed RIF NLCs are suitable
for pulmonary drug delivery. In-vitro release study showed
sustained drug release of RIF from spray dried NLCs.
• Cell internalization studies are required to conform efficacy of
ligand conjugated RIF NLCs over non conjugated RIF NLCs.
37. 7/18/2018
37
1. Lawlor, C., et al., Cellular targeting and trafficking of drug delivery systems
for the prevention and treatment of MTb. Tuberculosis (Edinb), 2011.
91(1): p. 93-7.
2. Maretti, E., et al., Inhaled Solid Lipid Microparticles to target alveolar
macrophages for tuberculosis. Int J Pharm, 2014. 462(1-2): p. 74-82.
3. Pham, D.-D., E. Fattal, and N. Tsapis, Pulmonary drug delivery systems
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I am grateful to my research guide Dr. (Mrs) Ujwala A. Shinde, Associate
Professor of Pharmaceutics for her invaluable guidance, encouragement and
advice during the research work.
I express my gratitude to Dr. (Mrs) Mangal S. Nagarsenker, Dr.
(Mrs) Mala D. Menon, Dr. (Mrs) Namita D. Desai for allowing use of various
instruments and apparatuses.
I am grateful to Lupin Ltd. (Mumbai), CIRCOT (Mumbai), SAIF Punjab
University (Chandigarh), Kelkar Education Trust's Scientific Research
Centre (Mumbai), Dept. of Nanoscience (University of Mumbai), Bharti
Vidyapreeth College of Pharmacy, Diya Lab, Ambernath Organics Pvt. Ltd.
(Mumbai), MKR Laboratories