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ragupathyrenganathan
Pharmacosome – A Spanking Accession in Vessicular Drug Delivery System
Formulation Discussion
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About Authors:
Swati Yadav1*, Dr. S.K Prajapati1
1institute of pharmacy,
Bundelkhand University, Jhansi
*swati3231@gmail.com

Abstract: 11, 12
Pharmacosome is a neoteric amelioration in the terrain of solubility improvement of drug. Pharmacosome is a spanking accession in the vesicular drug delivery system which exposition sundry precedence over conventional drug delivery. Pharmacosome are vesicular system amphiphillic in nature having drug phospholipid complex. Drug-lipid complex chemical structure may result into ultrafine, vesicular, miceller or hexagonal aggregates. Pharmacosome vesicular system enhances drug permeation through biomembrane resulting in improved bioavalibility as well as pharmacokinetic and pharmacodynamic properties of drug. Certain properties such as small size, predetermined entrapment efficiency, amphiphillicity, active drug loading and stability are major factor for its selectivity and precision.

Reference Id: PHARMATUTOR-ART-1993

Introduction:
Solubility known as major aspect for bioavailability enhancement. As solubility property is directly proportional to bioavailability of drug lower bioavailability, requiring some support to enhance solubility as bioavailability is determining factor for the rate and the extend of absorption. Vesicular system was such a support to bioavailability enhancement.

Vesicular drug delivery system13:
These are concentric lipid bilayer, when ampihillic building blocks come in contact of water result in vesicular system. Bingham in 1965nfirst reported the biological origin of vesicles. A vesicular structure encapsulates drug extending therapeutic index. Vesicular delivery system proves to be useful for

  • Liposomal entrapment
  • Facilitating better drug permeability and enhanced solubilisation
  • Decreased adverse effect and have better site specific targeting.

Though have certain limitation such as12:

Vesicular system

Features

Problem

Liposome

Microscopic vesicles (25mm to 100µm) of one or more lipid separated by water or aqueous buffer compartments

Expensive to prepare, degradation by oxidation, sedimentation,leaching of drug, lack of purity of natural phospholipids.

Niosomes

Non ionic surfactant vesicles

Aqueous suspension may exhibit aggregation, fusion, leaching or hydrolysis of entrapped drug (liminting the self life)time consuming inefficient, instability

Transferosomes

Suitable for both low and high molecular weight and also for lipophilic as well as hydrophilic drugs

Expensive, chemical instability due to oxidative degradation, lack of purity of natural phospholipids

Table 1: Conventional Vesicular system limitation

These are factor responsible for development of pharmacosome.

Pharmacosome11:
Pharmacosome can be defined as colloidal dispersion of drug covalently linked to lipid.theidea for the development of pharmacosome was based on surface and bulk interaction of lipid with water, Lipid-hydrogen, covalent or electrostatic binding. These are explained as coplex of phospholipid with amphiphilic, zwitterionic, stiochiometriccomplex of polyphenolic compound. Chemical structures of drug-lipid complex exist as ultrafine, vesicular, miceller or hexagonal (phospholipid – amphiphilic complex bearing active-H atom. A drug containing an active hydrogen atom or free carboxyl group (-OH, -NH2, -COOH) with or without a spacer chain can be esterified to the hydroxyl group of a lipid molecule, producing amphillic prodrug. Pharmacosome, facilitate membrane, tissue or cell wall transfer in the organism being amphiphillic property , reduces interfacial tension and mesomorphic behaviour at higher concentration, reduce surface tension result in increase contact area, thus increasing bioavailability of drug.

FIG 1: Targeting of drug and formation of pharmacosome

Advantage11, 12:
1.   Drug incorporation is high and predetermined
2.   It is covalently conjugate with lipid thus risk of drug lekage is minimal.
3.   Hydrophilic & lipophillic drug incorporation is advisable.
4.   Phase transition of temperature of vesicular and miceller pharmacosome have effect on their memberane interaction.
5.   Pharmacosome interact with biomembrane resulting in active ingredient transfer phase transition temperature of biomembrane caused by interaction improved membrane fluidity leading to enhanced permeation. Do not affect rate of release.
6.   Unentrapped drug can be removed speedily from formulation.
7.   A Physiochemical property of drug-lipid complex is responsible for its physiochemical stability.
8.   Reduced cost of therapy.
9.   Degradation of drug depend upon functional group of drug molecule, size, chain spacer and length of lipid.

Limitation of pharmacosome:
1.   For leakage protection of drug requires covalent bonding.
2.   Compound synthesis depends on amphiphillic nature.
3.   Pharmacosome require surface and bulk interaction of lipid with drug.
4.   Pharmacosome on storage undergoes aggregation, fusion as wellas chemical hydrolysis.

Component of pharmacosome11, 12:

Drug
Drug having a free carboxyl group or an active hydrogen (-OH,-NH2,-COOH) can be esterified to the lipid with or without spacer chain forming amphiphillic complex. Synthesised compound in turn provoking membrane, tissue or cell wall transfer in the organism so therapeutic efficiency of drug is enhanced i.e. pindolol maleate, bupranolol hydrochloride, taxol, acyclovir, etc.

Lipid
Lipid, phophatidylcholine are the major molecular building block of cell membrane. Drug on complexation with phospholipid which are hydrophobic or electrostatic zwitterionic molecule gives amphiphillic product which provide drugs to be lipid soluble and phospholipid, water soluble. Increase wetting and dispersion thus increasing solubility leading to enhanced bioavailability.

Solvent:
Solvent having volatile nature and high purity are being used. Solvent with intermediate polarity (between polarity of phospholipid and drug) is selected.

PARAMETER

Technique and instrument

Stability , formation of the complex

Infrared spectroscopy analysis, FTIR

Shape , size and surface morphology

Scanning electron microscopy (SEM), Transmission electron microscopy (TEM)

Solubility study

Shaking-flask method

Drug –excipient compatibility study

Thermo analytical technique , Differential scanning calorimetry  (DSC)

Degree of crystallinity

X-ray powder diffraction

In vitro dissolution studies

Dissolution test apparatus

Infrared spectroscopic analysis , nuclear magnetic resonance (NMR)

Formation of complex

Drug content

UV visible spectrophotometer

Table 2: Characterization parameter of pharmacosomes11


Fig 2: Method of preparation of pharmacosome11

Table 3: Research on pharmacosome

Researcher

Drug

Approaches

Gracia et al

ketoprofen

Increase solubility enhancement

Increase permeation of drug using dioeylphosphatidylcholine.

Muller-Goymann and Hamann4

fenoprofen

Increase solubility

JIN Yi Guang et al5

Acyclovir

Stability from heat, absorbed by plasma protein in blood decrease haemolytic reaction

Meihua HAN et al6

protopanaxadiol

Increased solubility ,stable

Zhang ZR et al7

3’,5’-dioctnoyl-5-fluoro-2’-deoxyuridine

AUC-10.97, Entrapment efficiency 96.62%, drug loading 29.02%

Shi et al8

Insulin phospholipid

Improve lipophillicity, improved oral absorption

Ping et al 10

5’-cholestrylsuccinyl-dideoxyinosine

Increased bioavailability, half life-7.64min

A Semalty et al1,2,3

Aceclofenac, diclofenac, asprin

Aceclofenac– increased release rate upto 79.78%(1:1) aceclofenac:phospholipid, 76.17% (1:2)

Diclofenac– increased releaseof pharmacosome to 87.8%, drug content 96.2±1.1%

Asprin- Drug content- 95.6% release rate increases after 10 hr upto 90.93.

Ping-fei Yue9

Geniposide

Increase absortion and permeationof biologically active constituents.

Reference:
1.Semalty A, Semalty M, Rawat BS, Singh D, Rawat MSM development and evaluation of pharmacosomes of aceclofenac. Indian Journal of Pharmaceutical Sciences, 2010;72: 576-81.
2.Semalty A, Semalty M, Singh D, Rawat MSM .Development and physicochemical evaluation of pharmacosomes of diclofenac. Acta Pharmaceutica, 2009;59: 335–44.
3.Semalty A, Semalty M, Rawat BS, Singh D, Rawat MSM. Development and Characterization of Aspirin-Phospholipid Complex for Improved Drug Delivery.International Journal of Pharmaceutical Sciences and Nanotechnology, 2010;3: 940-47.
4.Muller-Goymann CC, Hamann HJ. Pharmacosomes: Multilamellar vesicles consisting of Pure Drug. European Journal of Pharmaceutics and Biopharmaceutics, 1991;37: 113-17
5.Yiguang J, Tongc L, Ping A, Miao L, Houb XInternational Journal of Pharmaceutics, 2006; 309. Self-Assembled Drug Delivery Systems-Properties and In Vitro –Behaviour of Acyclovir Self-Assembled Nanoparticles (SAN). In Vivo: 199–207.
6.Han M, Chen J, Chen S, Wang X Preparation and study in vitro of 20(S)-protopanaxadiol pharmacosomes. Zhongguo Zhong Yao Za Zhi, 35: 842-6. 2010.
7.Yao Xue Xue Bao, Zhang ZR, Wang JX. Study on Brain Targeting 3′,5′-dioctanoyl-5-fluoro-2′-Deoxyuridine Pharmacosomes. 2001; 36: 771–6.
8.Cui F, Shi K, Zhang L, Tao A, Kawashima Y. Biodegradable Nanoparticles Loaded with Insulin-phospholipid Complex for Oral Delivery: Preparation, in vitro characterization and in vivo evaluation. Journal of Controlled Release, 2006; 114: 242-248
9.Yue P, Zheng Q, Wu B, Yang M, Zhang H. et al process optimization by response surface design and characterization study on geniposide pharmacosome pharmaceutical development and technology 2012;17(1):94-102.
10.Ping A, Jin Y, Da-wei C. Preparation and In Vivo Behavior of Didanosine Pharmacosomes in Rats. Chinese Journal of Pharmaceutics, 2005227–35:3. ;
11.Tanu goyal, ashwani singh rawat and meenakshi chauhan pharmacosomes: opening new doors for drug delivery international journal of pharmacy and pharmaceutical sciences ISSN- 0975-1491.
12.De pintu kumar, De arnad,pharmacosome : apotential vesicular drug deliverysystem international research journal of pharmacy 2012 ISSN2230-840.
13.Kavitha D, Naga sowjanya J, Shanker panaganti pharmacosomes: an emerging vesicular system volume 5, issue 3, november – december 2010; article-030 issn 0976 – 044x.



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