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“Bioavailability Enhancement of
Commonly Available
Class II and Class IV Drugs through
Surface Modification”
Submitted By:
Anshul Kestwal, Harshit Belwal, Latika Sharma and Ozair Ansari
CONTENTS
Introduction
Solubility Enhancement Methods
Drug Properties Data
Experimental Progress
Modification in Plan
Conclusion
References
INTRODUCTION
A PEEP INTO THE PROJECT BASICS
PROJECT OBJECTIVE
To select some cheaply available low solubility, low bio-
availability common class II and class IV drugs.
To enhance the amorphousness (surface area) of insoluble or
poorly soluble crystalline class II and class IV drugs via solvent
and anti-solvent routes.
To enhance the bio-availability of the above medicines via surface
modification observed through UV vis analysis.
PHARMACEUTICAL DRUGS
Chemical substances used for treating, curing and preventing different types of
diseases.
Commonly referred to as medicines or medication, pharmaceutical drugs are used
in the medical diagnosis, treatment, prevention or cure of disease.
Discovery and Development: an expensive endeavour.
Classified in various ways:
Usage
Solubility and Permeability
Potentiality of Abuse
CLASSES OF DRUGS
BIOPHARMACEUTICAL CLASSIFICATION SYSTEM
Solubility Permeability
High Low
High Class I Class III
Propanolol, Verapemil, Neomycin, Ranitidine, Peptites,
Metoproplol, Salicylic Acid, Enalprilate, Cetirizine, Folinic
Diazepam, Caffeine, Glucose Acid
Mefenamic
Paracetamol
from Zeldinac SP Acid from
Spasmonil Plus
Magnesium
Nimesulide
Hydroxide from
Freelex from Nicip
EXPERIMENTAL PROCEDURE I
1. In the first step, we powder the
drug using mortar-pestle. Then
we dissolve the powdered drug
in a solvent (ethanol or acetone
have been selected for these
drugs).
2. After dissolving it for about 10-
15 minutes, we filter the
solution. It is heated on hot
plate until crystals appear, and
then a minute quantity of
solvent is added to create a Figure 1: Solution of Figure 2: Solution of
saturated solution of drug in Mefenamic Acid in Mefenamic Acid being
solvent. Acetone filtered.
EXPERIMENTAL PROCEDURE II
1. We put the anti-solvent i.e. water in
the ultra-sonicator machine and add
filtered, saturated drug solution drop
by drop.
2. Sonication of the solution is done to
properly dissolve the medicine
solution in the anti-solvent, and notice
the effect of the ultrasonic
frequencies on the shape of the
precipitate.
3. After sonicating the solution, we keep
the solution at room temp to cool Figure 3: Solution being
down and for the precipitation of the sonicated with anti-
medicine. solvent in ultra-sonicator
EXPERIMENTAL PROCEDURE III
1. After the precipitation of the
medicine, we again filter the
solution and here, the
precipitate is the product
that we desire.
2. After separating the
precipitated drug from the
solution, we dry it and then
go for the XRD Analysis of
the particles of the
precipitate.
3. We shall also do UV Vis
Analysis for bio-availability.
Figure 4: Solution after being
sonicated with developed precipitates
MODIFICATION IN PLAN
TIMELINE
• In this case the API chosen was • Even after 48 hours, however, no
Paracetamol (Class II). 10ml of Solvent was crystallisation was witnessed
chosen and 2 gm of Paracetamol was
dissolved (in excess).
Solvent Solubility Solvent Volume Amount of
• The mixture was stirred using a magnetic Density taken API
required
stirrer at 400rpm and room temperature for
10 minutes. The solution was then allowed Ethanol 232.75 789 10 ml 1.836 gm
gm/kg kg/cu.m (7.89 gm)
for settling for 2 hours. The clear, saturated
solution was measured to be 8.9 ml.
• Having identified a preliminary method for Crystallisation using Anti Solvent, our
next steps will involve the following:
• Effects of Drop-rate, Agitation/Mixing, Solvent/Anti-Solvent Ratio, on Crystallization. We
identify this using different Drop-rate and Rotation velocity of Magnetic Stirrer.
• Micrograph, X-Ray Diffraction, FTIR, SEM, Bioavailability Tests, depending upon the
feasibility to identify the changes in Crystal Structure, Surface Characteristics,
Bioavailability, etc.
• This will lead to conclusion of experiment after factoring in the effect of multiple
variables and process streamlining vis a vis the most effective experimentation
methodology.
EXPERIMENTAL PHOTOS
SUMMARY
The oral bioavailability of BCS (biopharmaceutical classification system)
class II drugs with poor solubility and reasonable permeability is limited
by the drug dissolution step from drug products.
General parameters affecting solubility are particle size, shape and
surface area physicochemical properties of drugs, physical forms of
drugs, solvents, pH of the medium, temperature and use of surfactants.
In this Project, pharmaceutical particle technology is employed to
improve poor aqueous solubility of drug compounds that
limits in vivo bioavailability owing to their low dissolution rate in the
gastrointestinal fluids following oral administration.
By surface enhancements, the drugs considered will be made available
for ingestion, saving costs and other resources used in injection, and
providing a quicker and more effective treatment path.
REFERENCES
Plagiarism is Criminal.
REFERENCES
• “Major issues facing the pharmaceutical industry and their relationship to clinical pharmacy”, Drug Intell Clin Pharm. 1984
Jan;18(1):59-61.
• “Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal
Chemistry)”, Folkers G, van de Waterbeemd H, Lennernäs H, Artursson P, Mannhold R, Kubinyi H (2003).
• “Biopharmaceutics Classification System (BCS): Development, Implementation, and Growth”, Mehta M (2016).
• Charkoftaki, G., Dokoumetzidis, A., Valsami, G. and Macheras, P. (2010), “Biopharmaceutical Classification Based on Solubility and
Dissolution: A Reappraisal of Criteria for Hypothesis Models in the Light of the Experimental Observations”. Basic & Clinical
Pharmacology & Toxicology, 106: 168–172. doi:10.1111/j.1742-7843.2009.00506.x
• http://www.ijpsonline.com/articles/cocrystals-a-novel-approach-to-modify-physicochemical-properties-of-active-
pharmaceutical-ingredients.html?view=mobile
• http://www.drug-dev.com/Main/Back-Issues/SPECIAL-FEATURE-Bioavailability-Solubility-New-App-1265.aspx
• http://onlinelibrary.wiley.com/doi/10.1111/j.1742-7843.2009.00506.x/full
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399483/
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