Design And Development Controlled Release Micro Spheres Of Some Selected Anti-retroviral Drugs

DESIGN AND DEVELOPMENT CONTROLLED RELEASE MICROSPHERES OF SOME SELECTED ANTI-RETROVIRAL DRUGS

BY Agnimitra Dinda University Department of Pharmaceutical Sciences, Utkal University, Bhubaneswar

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AIDS :

INTRODUCTION :

Acquired Immuno Deficiency Syndrome Affected nearly 45 million people of in the world Characterized by : Various virus Replication CD4 lymphocyte depletion Immunodeficiency Therapy : HIV nucleoside reverse transcriptase inhibitors : Lamivudine , Abacavir,Didanocin Non nucleoside reverse transcriptase inhibitors : Navirapine, Delavaridine HIV protease inhibitors : Saquinaqvir, Indinavir, Ritonavir, Lopinavir, Nelfenavir Fusion inhibitors : Fuzeon

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Regimen : Viral replication effectively reverse CD4 cell depletion reduce morbidity & mortality

 Single dose form  Combination therapy Combination Therapy : Lamivudine and Stavudine  Lamivudine and Zidovudine  Lamivudin , Stavudine & Navirapin  Lamivudine , Zidovudine & Nevirapine Vital combination (World wide) : Combination of

 Nucleoside reverse transcriptase inhibitors Lamivudine and abacavir protease inhibitors Ritonavir and Lopinavir 3

DRUG PROFILE: MOA Abacavir :  prevent the conversion of viral RNA into proviral DNA before the entry in to host cell.

Ritonavir and Lopinavir :  Peptidomimetic HIV protease inhibitors  bind reversibly to active site of HIV protease  preventing the polypeptide synthesis and mutation.

Pharmacokinetic :  Half life nearly 1-5 hours  Bioavailability (50-60%)

Oral doses regimen : 

200mg twice a day 4

Back Ground of The Invention:

 Reduce the frequency of administration  To improve patient compliance  Increase bioavailability  So sustained or controlled release formulations of above drugs are desirable  Conventional oral dosage form available  Controlled release formulation absent  So controlled release formulation essentials

Controlled release drug delivery: Advantages:  Increase incidence and / or intensity of adverse effect and toxicity  Better drug utilization  More uniform drug utilization  More uniform blood circulation  Improve patient complience  Decrease dosing frequency more consistence and prolong therapeutic effect  A greater selectivity of pharmacological activity  Targeting the drug to a specific organ and tissue  Control the rate of delivery to the target tissue

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AIM & OBJECTIVE: To reduce dose To reduce the frequency of administration To improve patient complience To increase biological Half life To increase bioavailability To reduce the toxicity To increase loading and entrapment efficiency To study influence of formulations factors 6

PLAN OF WORK: Steps develops :  Preformulation Study  Physiocochemical characterization of drug  Solubility study of the drug in different physiological pH condition  Selection of dissolution medium  Drug-Excipient compatibility study  Design and Formulation of dosage forms  Preparation of Standard Curve  Preparation of dosage forms  Evaluation of dosage forms  % of yield calculation  Micromeritic properties  Particle size distribution  Flow properties  Mean particle size determination 7

PLAN OF WORK: Determination of % Drug entrapment efficiency SEM study FTIR study DSC study X-RD study In-vitro dissolution rate studies Dissolution rate kinetics studies Selection of final formulation Stability study In-Vivo Evaluation In-Vitro and In-Vivo Correlation

Content

&

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PROPOSED OUT COME:  The purpose formulation increase bioavailability, reduce the dose and reduce dosing frequency.  Formulation reduces side effect and toxicity.  It may provide prolong action with less toxicity and can be possible for marketed preparation .

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REFERENCES: 1.    Masur, H..Michelis., M.A. Greene., J.B. Onorate, et.al, An out break community acquired pneumo cystis carinii pneumonia : initial manifestation of cellular immuno dysfunction. N. Engl. J. Med., 1981,305: 1431-1438. 2.    Ho, D.D., A.U., Perelson, A.S., Chen., W., Leonard,J.M., and Markowitz, M. Rapid turn over of plasma vorions and CD4 lymphocytes in HIV infection. Nature, 1995, 373: 123-126. 3.     Pereson, A.S., Neumann, A.V., Markowitz, M., Leonard, J.M., and Ho, D.D. HIV-1 dynamic in vivo: virion clearance rate, infected cell life span, and viral generation time. Science, 1996,271, 1582-1586. 4. Pallela, F.J. Jr., Delaney, K.M., Moorman, A.C, Loveless, M.O., Fuhrer, J., Satten, G.A., Aschman. Decline morbidity and mortality among patient with advance immuno deficiendy virus infection. HIV out patient study infection, N. Engl. J. Med.,1998,338: 853-860. 5.       CIMS® India: Aprl-July, 2007, Page 427-430. 6.     Gao, W.Y., Agbaria, R., Drescoll, J.S., and Mitsuya, H. Divergent anti human deficiency virus activity and anabolic phosphorylation of 2’, 3’deoxynucleoside analogs in resting and activated human cells. J. Bio. Chem. 1994, 269: 12633-12638. 7.       S. Haznedar, B. Dortune, “ Preparation and In-vitro Evaluation of Eudragit microspheres containing acetazolamide”, International Journal of 10 Pharmaceutics, 269(2004)131-140. 8.      Sanju Dinwan, Anil Kumar Singla and Vivek Ranjan Sinha, “Evaluation of

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