Oral Bioavailability Enhancement Of Poorly Soluble And Poorly Permeable Drugs Using Self-Microemulsifying Drug Delivery Systems And The Effect Of Piperine
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Date
2010-01
Authors
Mallikarjun, Chitneni
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
There are approximately 40% of new drug molecules discovered and some drug
molecules that are available in the market, having poor bioavailability due to poor
solubility and/or poor permeability. The present study aimed at formulating a selfmicroemulsifying
drug delivery system (SMEDDS) using two BCS class IV drugs,
namely sulpiride and norfloxacin. Sulpiride is a P-gp substrate and norfloxacin is a
substrate of MRP2, BCRP and an unknown efflux pump. From the solubility studies
of drugs in various oils, surfactants and co-surfactants, oleic acid, Tween 80 and
propylene glycol were chosen to prepare SMEDDS formulations. Two formulations
were chosen for further study based on droplet size and solubility. The first
formulation consisted of 4.76% w/w of oleic acid, 63.49% w/w of Tween 80 and
31.75% w/w of propylene glycol, with a mean droplet diameter of 9.27 nm and drug
solubility of 22 mg/1000 mg for sulpiride, 9.57 nm and 17.33 mg/1000 mg for
norfloxacin respectively. The other formulation consisted of 17.71% w/w of oleic
acid, 55.14% w/w of Tween 80 and 27.15% w/w of propylene glycol, with a mean
droplet diameter of 85 nm and drug solubility of 32 mg/1000 mg for sulpiride, 92 nm
and 27.53 mg/1000 mg for norfloxacin. Isocratic HPLC- fluorescence methods were
developed and validated for the determination of sulpiride and norfloxacin in rat
intestinal perfusates and rabbit plasma separately. The in situ permeability
experiment was performed on three intestinal segments, duodenum, jejunum and
ileum in rats using single-pass perfusion technique. The SMEDDS formulation and
micellar solution exhibited significant increase in the effective permeability
coefficient of the drug across all the three intestinal segments compared with drug
solution for the two drugs. There was no significant difference in the effective
permeability coefficients values between SMEDDS formulation and micellar
solution for both drugs.
Description
Keywords
Selfmicroemulsifying drug delivery system , using sulpiride and norfloxacin