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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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INTRODUCTION:

AIDS :Acquired Immuno Deficiency SyndromeAffected nearly 45 million people of in the world

Characterized by :Various virus ReplicationCD4 lymphocyte depletion Immunodeficiency

Therapy :HIV nucleoside reverse transcriptase inhibitors : Lamivudine , Abacavir,DidanocinNon nucleoside reverse transcriptase inhibitors : Navirapine, Delavaridine HIV protease inhibitors :Saquinaqvir, Indinavir, Ritonavir, Lopinavir, NelfenavirFusion 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 abacavirprotease inhibitors

Ritonavir and Lopinavir

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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

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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

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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 formsPreparation of Standard CurvePreparation of dosage formsEvaluation of dosage forms

% of yield calculation Micromeritic properties Particle size distribution Flow properties Mean particle size determination

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Determination of % Drug Content & entrapment efficiency

SEM study FTIR studyDSC studyX-RD studyIn-vitro dissolution rate studiesDissolution rate kinetics studies Selection of final formulation Stability study In-Vivo EvaluationIn-Vitro and In-Vivo Correlation

PLAN OF WORK:

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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 Pharmaceutics, 269(2004)131-140.

8.      Sanju Dinwan, Anil Kumar Singla and Vivek Ranjan Sinha, “Evaluation of Mucoadhesive properties of chitosan Microspheres prepared by different methods”, AAPS Pharmtech. 2004, 5(4), Article 67.

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