DEVELOPMENT OF AMORPHOUS LIPID-POLYMER HYBRID FOR IMPROVED SOLUBILITY OF A POORLY-WATER SOLUBLE-DRUG: GLIBENCLAMIDE AS A MODEL DRUG
MUMUNI AUDU MOMOH1 , CALISTER ELOCHUKWU UGWU2, *, FRANKLIN CHIMAOBI KENECHUKWU1 , MUSILIU ADEDOKUN3 , AYODEJI AGBOKE3 , CHIBUZOR BEN AMADI2 , HYGINUS EZE1 , NAFIU AMINU4 , JAMES OYENIYI4 , ANTHONY AMAECHI ATTAMA1
1. Drug Delivery and Nanomedicines Research Unit, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu, Nigeria.
2. Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria.
3. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Uyo, Akwa Ibom, Nigeria.
4. Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto.
Afr. J Pharm Res Dev; Volume 12(1): 097-108 ; 2020
ABSTRACT
The use of glibenclamide in diabetes mellitus (DM) management is limited by poor aqueous solubility, dissolution rate, low bioavailability and short half-life. To address these problems, glibenclamide-loaded lipid-polymer hybrids (LPHs) were prepared. LPHs containing different ratios of beeswax and Eudragit® RS 100 as lipid and polymer, respectively, were prepared and characterized with respect to particle size, pH stability, encapsulation efficiency (EE %), loading capacity, in vitro release and in vivo bioactivity. The morphology and particle sizes showed smooth and spherical particles in the ranges of 14.22 ± 0.15 – 24.78 ± 0.31 µm, 8.84 ± 0.11 – 15.43 ± 0.16 µm, and 8.80 ± 0.11 – 11.00 ± 0.11 µm for X1 – X3, X4 – X6, and X7 – X9, respectively. The pH was stable without drug degradation. EE (%) of the LPHs ranged between 78.60 ± 0.02 – 95.40 ± 0.11 %, 91.33 ± 0.23 – 97.58 ± 0.17 %, and 89.66 ± 0.13 – 97.80 ± 0.18 % for X1 – X3, X4 – X6, and X7 – X9, respectively. In vitro release of the LPHs showed T40 (time to release 40 % of the drug) at 4, 12, 0.5, 0, 12, 0.5, 0, 0, and 12 h for X1 – X9, respectively. Maximum blood glucose lowering (≈ 60 ± 22.6 mg/dl) was obtained in the LPHs, which was significant (p < 0.05) when compared to a commercial brand (69 ± 18.32 mg/dl). This study showed that LPHs is a promising alternative method for the delivery of a model poorly aqueous-soluble drug, glibenclamide.
Email of correspondence:calister.ugwu@unn.edu.ng;
KEYWORDS: Lipid-polymer hybrids; Antidiabetics; Hepatotoxicity; Glibenclamide; Blood glucose level; Beeswax.