Pharmacosomes

Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids, and may exist as ultrafine vesicular, micellar, or hexagonal aggregates, depending on the chemical structure of drug-lipid complex.

1. Pharmacosomes Mr. Sagar Kishor Savale [Department of Pharmaceutics] [email protected] 2015-2016 Department of Pharmacy (Pharmaceutics) | Sagar savale

2. CONTENTS Introduction Importance Formulation Evaluation Applications Conclusion References 6/7/2016 sagar kishor savale 2

3. INTRODUCTION Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids, and may exist as ultrafine vesicular, micellar, or hexagonal aggregates, depending on the chemical structure of drug-lipid complex. Pharmacosomes are amphiphilic phospholipid complexes of drugs bearing active hydrogen that bind to phospholipids. Pharmacosomes impart better biopharmaceutical properties to the drug, resulting in improved bioavailability. Pharmacosomes have been prepared for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. Developing the pharmacosomes of the drugs has been found to improve the absorption and minimize the gastrointestinal toxicity.   6/7/2016 sagar kishor savale 3

4. Pharmacosome 6/7/2016 sagar kishor savale 4

5. In pharmacosomes , membrane fluidity depends upon the phase transition temperature of the drug lipid complex, but it does not affect release rate since the drug is covalently bound. The drug is released from pharmacosome by hydrolysis (including enzymatic). The physicochemical stability of the pharmacosome depends upon the physicochemical properties of the drug-lipid complex. Following absorption, their degradation velocity into active drug molecule depends to a great extent on the size and functional groups of drug molecule, the chain length of the lipids, and the spacer. They can be given orally, topically, extra-or intravascularly . 6/7/2016 sagar kishor savale 5

6. IMPORTANCE Pharamcosomes have some importance in escaping the tedious steps of removing the free unentrapped drug from the formulation Pharmacosomes provide an efficient method for delivery of drug directly to the site of infection, leading to reduction of drug toxicity with no adverse effects and also reduces the cost of therapy by improved bioavailability of medication, especially in case of poorly soluble drugs. Pharmacosomes are suitable for incorporating both hydrophilic and lipophilic drugs . Entrapment efficiency is not only high but predetermined, because drug itself in conjugation with lipids forms vesicles. 6/7/2016 sagar kishor savale 6

7. There is no need of following the tedious, time-consuming step for removing the free, unentrapped drug from the formulation. Since the drug is covalently linked, loss due to leakage of drug, does not take place. No problem of drug incorporation Encaptured volume and drug-bilayer interactions do not influence entrapment efficiency, in case of pharmacosomes . 6/7/2016 sagar kishor savale 7

8. PREPARATION Two methods have been used to prepare vesicles : 1 . The hand-shaking method 2. The ether-injection method In the hand-shaking method, the dried film of the drug–lipid complex (with or without egg lecithin) is deposited in a round-bottom flask and upon hydration with aqueous medium , readily gives a vesicular suspension. In the ether-injection method, an organic solution of the drug–lipid complex is injected slowly into the hot aqueous medium , wherein the vesicles are readily formed. 6/7/2016 sagar kishor savale 8

9. EVALUATION OF PHARMACOSOMES Solubility Drug content Entrapment efficiency Dissolution study Scanning electron microscopy (SEM ) Differential scanning calorimetry (DSC ) X-ray powder diffraction (XRPD) 6/7/2016 sagar kishor savale 9

10. APPLICATIONS The approach has successfully improved the therapeutic performance of various drugs i.e. pindolol maleate, bupranolol hydrochloride, taxol , acyclovir, etc. The phase transition temperature of pharmacosomes in the vesicular and Micellar state could have significant influence on their interaction with membranes. Pharmacosomes can interact with bimembranes enabling a better transfer of active ingredient. This interaction leads to change in phase transition temperature of bimembranes thereby improving the membrane fluidity leading to enhance permeations. 6/7/2016 sagar kishor savale 10

11. Amphiphilic Prodrug Pharmacosomes of Aceclophenac Pharmacosomes of Diclophenac Pharmacosomes of Didnosine Pharmacosomes of Acyclovir APPLICATIONS 6/7/2016 sagar kishor savale 11

12. References Y . Jin et al., "Self-Assembled Drug Delivery Systems-Properties and In Vitro – In Vivo Behaviour of Acyclovir Self-Assembled Nanoparticles (san)," Int. J. Pharm. 309 (1–2), 199–207 (2006). P . Goyal et al., "Liposomal Drug Delivery Systems: Clinical Applications," Acta Pharm . 55, 1–25 (2005). H.A . Lieberman, M.M. Rieger , and G.S. Banker, Pharmaceutical Dosage Forms: Disperse Systems (Informa Healthcare, London, England, 1998), p. 163. S.S . Biju et al., "Vesicular Systems: An Overview," Ind. Jour. Pharm. Sci. 68 (2), 141–153 (2006). M.O . Vaizoglu and P.P. Speiser , "Pharmacosomes—A Novel Drug Delivery System," Acta Pharm. Suec . 23, 163–172 (1986). A . Singh and R. Jain, "Targeted Vesicular Constructs For Cytoprotection and Treatment of H. Pylori Infections," US Patent 6576,625 (2003). I.P . Kaur and M. Kanwar , "Ocular Preparations: The Formulation Approach," Drug Dev . Ind. Pharm. 28 (5), 473–493 (2002). F . Volkering et al., "Influence of Nonionic Surfactants on Bioavailability and Biodegradation of Polycyclic Aromatic Hydrocarbons," App. Environ. Micro. 61 ( 5), 1699–170 (1995 ). A . Steve, "Lipophilic Drug Derivatives for Use in Liposomes," US Patent 5534499 ( 1996). 6/7/2016 sagar kishor savale 12