Development Of Ketoprofen Loaded Proliposomal Powders For Improved Gastric Absorption And Gastric Tolerance: In Vitro And In Situ Evaluation

1208 words - 5 pages

Pearlitol SD 200 based proliposomes
Ketoprofen proliposome formulations using pearlitol SD 200 and different ratios of HSPC and cholesterol were prepared. HSPC (a high phase transition temperature lipid) and cholesterol (for structural rigidity) were selected because of their lower risk of oxidation and improved stability of liposomes respectively. However any variation in the composition of HSPC and cholesterol results in the deformation of vesicle, which leads to drug leakage and fusion of vesicle with gastrointestinal epithelium (32). To conquer the lipid to cholesterol composition in developing stable proliposomes varying ratios of HSPC to cholesterol (total lipid mixture of 250 µM) were investigated.
Physicochemical characterization of proliposomes
Formation of liposomes from proliposomal powders
Stepwise formation of liposomes from proliposomes upon hydration was observed under optical microscope and represented in Figure 2 A-D. Proliposomal powder (Figure 2A) upon contact with distilled water resulted in the formation of tubular structures (Figure 2B) due to instantaneous surface lipid hydration of proliposomes followed by budding off and liposome formation until the surface lipid hydration and solubility of the water soluble carrier ends. The hydrophilic nature of pearlitol might also facilitate the quick hydration of proliposomes to transform into liposomes. Under stagnant conditions (without agitation) liposomes formed are aggregates as shown in Figure 2C. Optical microscopic images of the liposomes formed upon hydration with manual agitation (Figure 2D) confirms separation of liposomes from aggregates and dispersion of spherical shape liposomes in the medium.
Micromeritics
Oral administration of proliposomal powders which forms liposomes in situ is a simple approach and resolves the stability problems associated with liposomal aqueous dispersion. Moreover proliposomal powders can provide dosing accuracy and also can be formulated in to commercially feasible solid unit dosage forms such as directly compressed tablets or filled hard gelatin capsules. Flow characteristics of the proliposomal powders are prime parameter in handling and processing of solid dosage forms. Optimal amount of solid carrier to coat the lipid mixture plays a major role in having good flow properties. Based on our previous observations and reports it is evident that 1 gm of inert carrier for 1 mM of total lipid was sufficient to produce the proliposomes with desirable flow properties (31,33). Flow properties for developed proliposomal formulations were assessed from Carr’s compressibility index and Hausner’s ratio and the results were listed in Table 2. Usually non coherent masses possess Carr’s compressibility index and Hausner’s ratio values of less than 21 and 1.25 respectively. The present results indicate fair to passable flow behavior for KPL0, KPL4 and KPL5, whereas KPL3 (equimolar ratio of lipid to cholesterol) shown desirable flow characteristics. KPL1 and...

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