Abstract
To enhance the dissolution and oral bioavailability of poorly water-soluble biphenyl dimethyl dicarboxylate (BDD), the supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed by adding a water-soluble polymer PVP to prevent precipitation of the drug and maintain a supersaturate state in vivo. Ternary phase diagrams were drawn to evaluate the microemulsification domain. The formulations were characterized by testing the physical stability of the drug, particle size and zeta potential. The pharmacokinetic study in beagle dogs was performed for the S-SMEDDS, SMEDDS formulation and the market drop pills. The optimized S-SMEDDS formulation consist of 35% (w/w) Cremphor EL35, 33% (w/w) Transcutol HP, 30% (w/w) MCT and 2% (w/w) PVPK30 of each excipient showed minimum mean droplet size (37.71 ± 0.87nm) and optimal drug release profile and better physical stability in water compared with the PVP absent SMEDDS. The in vivo studies showed that S-SMEDDS had significantly increased the Cmax and area under the plasma concentration-time curve (AUC) (P < 0.01). The S-SMEDDS formulation should be an effective oral dosage form for improving oral bioavailability of water-insoluble BDD.
Highlights
Chronic hepatitis B is one of the serious diseases that threaten human health, the researchers were seeking for an effective therapy medicine ongoing in recent years
hydroxypropyl methylcellulose (HPMC) was used to generate a supersaturated state and crystallization of drug was inhibited in S-self-microemulsifying drug delivery systems (SMEDDS) by Gao P (Gao & Morozowich, 2006; Gao et al, 2009), Studies on the mechanism responsible for inhibiting crystallization of drugs in aqueous solutions containing HPMC suggests that the polymer chain may inhibit nucleation, as well as crystal growth by adsorption of the HPMC molecules onto the surface of the nuclei, or onto the surface of crystals (Miller et al, 2008; Gao et al, 2003; Kim & Choi, 2002)
Polymer polyvinyl pyrrolidone (PVP) was selected as precipitate inhibitor which showed better physical stability with less amount of surfactant compared with the SMEDDS
Summary
Chronic hepatitis B is one of the serious diseases that threaten human health, the researchers were seeking for an effective therapy medicine ongoing in recent years. The conventional SMEDDS are isotropic mixtures of an oil, surfactant, cosurfactant and drug They form fine oil-in-water microemulsions less than 100nm when introduced into aqueous media under mild agitation in 37 °C (Pouton, 1997). If the partition coefficient of the drug for the SMEDDS microemulsion particle is such that the solubility of the drug is exceeded in the aqueous phase, the drug could precipitate following dilution with water, and this could result in poor performance in vivo. A high level of the surfactant was added to conventional SMEDDS formulations in order to prevent precipitation of the drug following dilution with water in the gastrointestinal (GI) tract and, in some cases, the surfactants can lead to an increased incidence of GI side effects, especially for patients with chronic disease. The optimized S-SMEDDS formulation was developed to improve the solubility and bioavailability of BDD and might bring higher efficacy and safety of oral BDD for a long term
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