BIOAVAILABILITY AND METHODS OF ENHANCING

BIOAVAILABILITY

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Presented by SHAHEEN BEGUM

Hallticket No:10S91R0035UNDER THE GUIDANCE OF

Associate Professor. Syed Mohammed KazimNizam Institute of Pharmacy & Research Centre

Deshmukhi (V), Nalgonda.AFFILIATED TO JNTUH.

CAUSES OF LOW BIOAVAILABILITY

First pass metabolismPoorly water soluble, slowly absorbing oral drugsInsufficient time for absorption in GITPoor dissolution (highly ionized and polar)Age,stress,disorders,surgery etcChemical reactions Metabolism by luminal microflora

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Methods of Enhancing Bioavailability

1.Enhancement of drug solibulity:

a. Micronization

b. Nanonization

c. SFR

d. SFL

e. EPAS

f. Use of surfactants

g. Molecular encapsulation with cyclodextrins

h. Eutectic mixtures5

2. Enhancement of drug permeability a. Lipid technologies

b. Ion Pairing

c. Penetration enhancers

3. Enhancement of drug stabilityd. Enteric coating

e. Complexation

f. Use of metabolism inhibitors

4. Enhancement of gastrointestinal retention a. GRDDS

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OPTIZORB TECHNOLOGY

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• Optizorb® technology is a combination of ingredients, which work together to speed up the rate at which the paracetamol tablet disintegrates and dissolves in the stomach.

• contains paracetamol 500mg along with super-disintegrants.• The new combination disperses five times faster and is absorbed 37% faster than standard

tablets.

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HOT-MELT EXTRUSION TECHNOLOGYThe development of novel drugs with poor solubility and bioavailability brought the application of HME into the realm of drug-delivery systems.HME involves the application of heat, pressure and agitation through an extrusion channel to mix materials together, and subsequently forcing them out through a die.HME extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier, increasing dissolution rates and bioavailability.

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ENHANCEMENT OF BIOAVAILABILITY BY INCREASING PERMEABILITY THROUGH

PHYSIOLOGICAL BARRIERS

NANOPARTICLE SYSTEMS WITH CHELATION AGENTS:

Increased BBB permeability and lower toxicityNanoparticles made of natural or artificial polymers ranging in size from about 10–1000 nm and present a possible tool to transport drugs across the BBBThe advantages of nanoparticles include reduced drug toxicity, improved biodistribution and therapeutic efficacyThe mechanism by which the nanoparticles deliver drugs into the brain may be involved in the preferential absorption of ApoE and/or B.The particles also appear to mimic LDL and interact with the LDL receptor, resulting in their uptake by brain endothelial cells

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BIOAVAILABILITY ENHANCEMENT BY BBB

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Fighting Alzheimer's disease with nanotechnology

PLAQUE

FORMATION OF FIBRILS

BETA AMYLOID PEPTIDES

1 •the nanotechnology-enabled approaches are being developed for early detection and accurate diagnosis of Alzheimer's, its therapeutic treatment, and prevention

2 •Alzheimer’s disease is among the most common brain disorders affecting the elderly population the world over

3 •This technique makes use of gold nanoparticles (NPs) and magnetic microparticles suspended in solution

BREAKING THROUGH TO THE BRAIN, TO DELIVER A CURE FOR PARKINSON’S

Nanotechnology uses a microscopic “bubble” transport systemit enables drugs to traverse the normally uncrossable blood brain barrier. Vesicles are one of the few things in the body that can permeate the BBB, however, pathogens are able to break down the BBB, enabling substances such as bacteria or other toxins to attack parts of the brainThe nanovesicles are highly stable and provide a controlled release mechanism TIGHT JUNCTION

GLIAL CELLS Nano bubble releasing drug

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REFERENCES

• D.M. BRAHMANKAR SUNIL B. JAISWAL Biopharmaceutics and pharmacokinetics a Treatise,Second Edition..Page No:345-363

• CVS SUBRAHMANYAM. Text book of Biopharmaceutics and pharmacokinetics .• shergill• http://archive.ispub.com/journal/the-internet-journal-of-aesthetic-and-antiaging-medicine/

volume-2-number-1/phytosomes-the-emerging-technology-for-enhancement-of-bioavailability-of-botanicals-and-nutraceuticals

• Wilson CG, Clarke CP, Starkey YY, Clarke GD. Comparison of a novel fast-dissolving acetaminophen tablet

• Martin physical pharmacy and pharmaceutical sciences 5th edition• Leon shargel.applied biopharmaceutics and pharmacokinetics• Pharmacokinetic and Bioequivalence Study Evaluating a New Paracetamol/Caffeine

Formulation in Healthy Human Volunteers Dongzhou J. Liu1 *, Mitchell Kotler1 and Scott Sharples2 1Medical Affairs and New Products Research and Development, GlaxoSmithKline, Parsippany, NJ 07054, USA 2Celerion, 2420 W Baseline Rd, Tempe, AZ 85283, USA

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• Wilson CG, Clarke CP, Starkey YY, Clarke GD. Comparison of a novel fast-dissolving acetaminophen tablet

• Martin physical pharmacy and pharmaceutical sciences 5th edition• Leon shargel.applied biopharmaceutics and pharmacokinetics 4th Edition.• Pharmacokinetic and Bioequivalence Study Evaluating a New

Paracetamol/Caffeine Formulation in Healthy Human Volunteers Dongzhou J. Liu1 *, Mitchell Kotler1 and Scott Sharples2 1Medical Affairs and New Products Research and Development, GlaxoSmithKline, Parsippany, NJ 07054, USA 2 Celerion, 2420 W Baseline Rd, Tempe, AZ 85283, USA

• Milogibaldi, Biopharmaceutics and clinical pharmacokinetics 4th Edition Page no 146.

• Venkateshwarlu, Fundamentals of Biopharmaceutics and pharmacokinetics Page no 331.

• Remington’s Pharmaceuticals sciences volium 1 Page no 1037• Remington’s Pharmaceuticals sciences volium 1 Page no 1041• Robert E Notary, Biopharmaceutics and pharmacokinetics.• Indian Journal of Pharmaceutical sciences. 15

REFERENCES

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Any Questions?