Solubilization of piperine from pepper fruit powder with hydrophilic lipid treatment: An alternative approach for traditional extraction methods

Piperine (PI), a pungent alkaloid from Piper nigrum Linn and Piper longum Linn. [1], is shown to enhance the bioavailability of various structurally and therapeutically diverse drugs [2, 3] and is a promising bioenhancer. Its partial aqueous solubility limits its oral absorption. Methods used for extraction of PI suffers from drawbacks like use of organic solvents, poor extraction efficiency and costly. In this report, effort is taken to prepare aqueous solution of PI from pepper fruits by simple method of pretreatment with hydrophilic lipid-Gelucire 44/14 (G44). Long pepper powder was mixed with molten mass of G44at 45–50°C, cooled and added measured volume of water (PG). Powder:G44 ratio optimization and PI content determination in PG and alcoholic extract were performed by HPTLC. Bioenhancing activity of the PG was compared with alcoholic extract and pure PI by giving its pretreatment to Wistar rats at different doses (10 and 20mg/kg) for different duration (3 and 7 days). Effects on exsorption of ornidazole, a P-gp substrate, in in vitro everted rat intestine (duodenum and ileum) was investigated [4,5] after pretreatment. Exsorption of ornidazole at mucosal surface in medium was monitored by RP-HPLC method for 90min. Powder:G44; 1:0.5 gave 2.38% PI which was considered optimized ratio for study and alcoholic 2.26%. In vitro study showed significant differences in exsorption of ornidazole. PG encompassed more bioenhancing activity than alcoholic extract (P<0.001), but comparable with pure PI (P>0.05) which may be attributed to self emulsifying and pseudosolubilization properties of G44(6). Dose dependent decrease in exsorption was observed but no effect of pretreatment duration. Use of G44 for solubilization of actives from crude source is less time consuming, effective and good alternative for other extraction methods.

Table 1. PI content in different solutions by HPTLC.

Solution		PI content µg/100µg of powder±S.D. (n=3)
Alcoholic extract solution		2.26±0.03
Long pepper powder: G44 (PG)	1:0.25 1:0.5 1:0.75 1:1 1:1.5 1:2	1.62±0.07 2.38±0.04 2.41±0.03 2.49±0.05 2.53±0.05 2.52±0.04

Acknowledgements: Vice Chancellor, Bharati Vidyapeeth University and Principal, Poona College of Pharmacy, Erandwane, Pune, India.

References: 1. Trease, G. E., Evans, W. C. Pharmacognosy. Baillere Tindall, London. 2. Atal, C.K. et al. (1981)J Ethnopharmacol 4:229–232. 3. Velpandian, T. et al. (2001) Eur J Drug Metab Pharmacokine 26:241–247. 4. Yumoto, R. et al. (1999) The Journal of Pharmacology and Experimental Therapeutics. 289:149–155. 5. Rao, Y.M. et al. (2006) Drug Metabol Drug Interact. 22:67–77. 6. Pillay, V., Fassihi, R. (1999) Pharm Res 16:333–337.