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Sustained-Release Glibenclamide-Loaded Solid Lipid Microparticles from Micellar Solutions of Homolipids

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Abstract

Purpose

Fat from Capra hircus (goat fat) has been widely used for drug delivery.

Methods

In this work, 1:1, 1:2, and 2:1 of goat fat and Softisan® 142 were melted together, cooled at room temperature, and the resultant matrix further modified with Phospholipon 90G (4:1) to obtain solidified reverse micellar solutions (SRMS). SRMS were used to prepare solid lipid microparticles (SLMs) loaded with or without glibenclamide, a poorly water soluble antidiabetic drug by hot melt homogenization. Particle size, morphology, thermal behavior, drug encapsulation efficiency, in vitro release study, and in vivo fate in diabetogenic rats were investigated.

Results

We report here an improved drug holding capacity (70.35%) of the lipid matrix of SRMS 2:1 due to imperfection of the lipid mixtures showing lower transition temperatures (117.0 °C) and enthalpies (−12.5 mW/mg). In vitro drug diffusion showed 66.98% drug release from SLM 2:1 exhibiting non-Fickian diffusion model (anomalous behavior) and almost zero-order kinetic. SLM 2:1 also gradually released 56.98% of glibenclamide under 16 h and maintained a steady state till 24 h; generally lowering blood glucose from 600 to 120 mg/dL unlike SLM 1:2 which showed burst glibenclamide release of 22.66% within 30 min with consequent rise in blood sugar.

Conclusion

The 2:1 micellar solution (SRMS) of homolipids could deliver glibenclamide in a sustained form better than the conventional tablet form.

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Acknowledgements

We thank Phospholipid GmbH Kӧln, Germany, BASF Ludwigshafen, Germany, and Gattefossé, St. Priest, France, for gift samples of Phospholipon® 90G. We equally thank JUHEL Pharmaceuticals for the gift sample of glibenclamide.

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Authors and Affiliations

  1. Drug Delivery and Nanomedicine Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria

    P. O. Nnamani, E. C. Ibezim, M. U. Adikwu & A. A. Attama

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  1. P. O. Nnamani
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  2. E. C. Ibezim
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  3. M. U. Adikwu
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  4. A. A. Attama
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Correspondence to P. O. Nnamani.

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Statement of Animal Rights and Use Protocols

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The animal studies were performed after receiving approval of the Animal Care and Use Committee of the Faculty of Pharmaceutical Sciences (ethical approval number: FP/PT/019/A/010). Clinically normal male albino Wistar rats weighing 200 ± 10 g, procured from the animal breeding center, Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka and housed in a regulated environment (25 ± 2 °C, 12 h light/dark cycle, light period starting at 7 am), acclimatized for 1 week prior to study and provided free access to standard rodent pellets (Guinea feeds Ltd Nigeria) and water in clean glass water bottles ad libitum, were used for the experiment. All animal experiments complied with the ARRIVE guidelines and were performed in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments. Cage-side clinical observations of the rats were made throughout the study period. The rats were divided into nine groups of five rats each and fasted overnight prior to the induction of diabetes mellitus.

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Nnamani, P.O., Ibezim, E.C., Adikwu, M.U. et al. Sustained-Release Glibenclamide-Loaded Solid Lipid Microparticles from Micellar Solutions of Homolipids. J Pharm Innov 17, 701–711 (2022). https://doi.org/10.1007/s12247-021-09554-5

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