About Authors:
Swati Yadav1*, Dr. S.K Prajapati1
1institute of pharmacy,
Bundelkhand University, Jhansi
*[email protected]
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 enhancementIncrease 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. |
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