BIOAVAILABILITY AND METHODS OF ENHANCING BIOAVAILABILITY 1 Presented by SHAHEEN BEGUM Hallticket No:10S91R0035 UNDER THE GUIDANCE OF Associate Professor. Syed Mohammed Kazim Nizam Institute of Pharmacy & Research Centre Deshmukhi (V), Nalgonda. AFFILIATED TO JNTUH.

OBJECTIVES OF BIOAVAILABILITY  Primary stages of developement of dosage form.  Determination of influence of excipients on absorption.  Development of new formulation.  Control of quality of drug Product PURPOSE  Approval of drug product  To characterize pharmacokinetics of new formulation.  To define the effects of physico chemical properties.  Effect of drug on pharmacokinetics

TYPES OF BIOAVAILABILITY 4 1.Pharmacokinetic Methods a. Plasma Level: Time Studies b. Urinary Excretion studies 2.Pharmacodynamic Methods a. Acute Pharmacological Response b. Therapeutic Response MEASUREMENT OF BIOAVAILABILITY  Absolute bioavailability:Oral Compared With I.V  Relative bioavailability: Oral Compared with oral standard

CAUSES OF LOW BIOAVAILABILITY  First pass metabolism  Poorly water soluble, slowly absorbing oral drugs  Insufficient time for absorption in GIT  Poor dissolution (highly ionized and polar)  Age,stress,disorders,surgery etc  Chemical reactions  Metabolism by luminal microflora

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 mixtures 6

2. Enhancement of drug permeability a.Lipid technologies b.Ion Pairing c.Penetration enhancers 3. Enhancement of drug stability a.Enteric coating b.Complexation c.Use of metabolism inhibitors 4. Enhancement of gastrointestinal retention a. GRDDS 7

BIOAVAILABILITY ENHANCEMENT BY BBB 8

OPTIZORB TECHNOLOGY 9

HOT-MELT EXTRUSION TECHNOLOGY  The 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. 10

ENHANCEMENT OF BIOAVAILABILITY BY INCREASING PERMEABILITY THROUGH PHYSIOLOGICAL BARRIERS Nanoparticle systems with chelation agents: increased BBB permeability and lower toxicity  Nanoparticles made of natural or artificial polymers ranging in size from about 10–1000 nm and present a possible tool to transport drugs across the BBB  The advantages of nanoparticles include reduced drug toxicity, improved biodistribution and therapeutic efficacy  The 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, and. The transferrin transcytosis systems may be also employed by the particulated drug delivery systems to deliver drugs into the brain.If an iron chelator can be covalently bonded to a nanoparticle, the particle may serve as a targeting vehicle to deliver the chelator to the brain and cross the BBB. 11

Fighting Alzheimer's disease with nanotechnology  Alzheimer’s disease is among the most common brain disorders affecting the elderly population the world over  some of the nanotechnology-enabled approaches that are being developed for early detection and accurate diagnosis of Alzheimer's, its therapeutic treatment, and prevention.  This technique makes use of gold nanoparticles (NPs) and magnetic microparticles suspended in solution, both of which are conjugated with an antibody specific to ADDLs while each gold NP is also attached to a large number of "barcode DNA.  The BBB Performs the beneficial function of keeping "foreign substances" like disease-causing agents and toxins circulating in the blood from getting into the brain, but, at the same time, also stops the transport of most large active molecules, even those of possibly therapeutic value, into brain tissue.  designing nano-scale "carriers" endowed with desirable surface properties are being investigated to facilitate the efficient, targeted and safe delivery of active molecules across the BBB and their sustained release in the brain. 12

BREAKING THROUGH TO THE BRAIN, TO DELIVER A CURE FOR PARKINSON’S  Nanotechnology uses a microscopic “bubble” transport system that can bring drugs to the exact area in the body where they are needed, rather than administering them through the bloodstream or directly to the central nervous system, which can cause side effects.  It offers the best hope for curing brain and central nervous system diseases because it enables drugs to traverse the normally uncrossable blood brain barrier. . Vesicles occur naturally in the body and are used to carry proteins and other molecules through membranes. Vesicles are one of the few things in the body that can permeate the BBB, which consists of special cells around the central nervous system to keep blood and brain fluid separate.  however, pathogens are able to break down the BBB, enabling substances such as bacteria or other toxins to attack parts of the brain — possibly resulting in diseases such as meningitis, multiple sclerosis, Alzheimer’s, Parkinson’s, and HIV Encephalitis.  The nanovesicles are highly stable and provide a controlled release mechanism which allows the drug to pass through biological barriers, including the blood-brain barrier, targeting specific cells and tissues. 13

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