Formulation and clinical investigation of optimized vinpocetine lyoplant-tabs: new strategy in development of buccal solid dosage form

Abstract

BackgroundThis work aimed to develop a new solid dosage formulation of vinpocetine (VPN) in the form of buccal freeze-dried pullulan-based tablets (lyoplant-tabs) loaded with physically modified drug binary system.MethodsDifferent polyvinyl pyrrolidone (PVP) grades were studied to prepare an efficient VPN binary system characterized by enhanced equilibrium saturation solubility, solubilization efficiency, thermodynamic stability, and permeation through oral mucosal cell lines. The concentrations of pullulan and swelling-aid polymer that affect the quality attributes of lyoplant-tabs were optimized. Clinical pharmacokinetics study on human volunteers for the optimized lyoplant-tabs compared to marketed product was accomplished.ResultsA promising drug binary system with polyvinyl pyrrolidone vinyl acetate (PVP-VA64) utilizing the lyophilization technique was developed. Solid-state characterization confirmed transformation of VPN completely into the amorphous form. The concentrations of pullulan and swelling-aid polymer were significantly affecting the characteristics of the tablets. Compared to the commercial VPN tablets, pullulan-based buccal tablets demonstrated enhancement in the studied pharmacokinetic parameters with positive impact on the drug bioavailability.ConclusionThese VPN lyoplant-tabs containing lyophilized PVP-VA64-VPN binary system can be considered as an alternative to currently available marketed tablets; however, further preclinical investigations using large number of volunteers are required.

<p>Enhancement of Simvastatin ex vivo Permeation from Mucoadhesive Buccal Films Loaded with Dual Drug Release Carriers</p>

“…To evaluate the process of SMV solubilization in an aqueous media of HP β-CD at different concentrations, Gibbs free energy of transfer (ΔGtr°) was calculated to indicate whether the process is appropriate or not. 14,47,48 Results for ΔGtr°of SMV in an aqueous solution of HP β-CD at 25°C indicated marked change from −1261.35 to −8214.49 (J/mol) when the HP β-CD molar concentration was increased from 2 to 20 mM. The obtained negative values indicated spontaneous thermodynamic reaction between SMV and HP β-CD molecules in the aqueous medium.…”

“…The latter is obtained when the solubility of the drug is increased with increasing the polymer concentration up to a certain limit followed by a plateau. 14 The former (type A) may be further classified into A L and A P types. When the drug solubility is increased upon increasing the concentration of the polymer, and the complex formed is first order with respect to the polymer and first or higher order with respect to the drug, type A L is formed.…”

“…Previous study has also indicated enhancement in the rate of vinpocetine permeation across the buccal oral epithelial cells from a drug complex, in the form of solid dispersion with polyvinyl pyrrolidone vinyl acetate, when compared to pure vinpocetine solution. 14…”

“…10 Reduction in drug's particle size by micronization and nanosuspension formation, crystalline change by polymorph and amorphous/crystalline modifications, drug dispersion in hydrophilic carriers (solid dispersions), solid solutions and cryogenic methods are examples of physical modifications. [11][12][13][14][15] Derivatization, salt formation and complexation are common types of chemical modifications. 16,17 Cosolvency, hydrotropes, addition of surfactants and solubilizers, and supercritical fluid technology are good examples of other modifications.…”

Improved Transmucosal Delivery of Glimepiride via Unidirectional Release Buccal Film Loaded With Vitamin E TPGS-Based Nanocarrier

“…The release of GMD from the prepared films and its permeation through buccal mucosa was carried out using a modified USP dissolution test apparatus (Pharma test). 21 , 22 A buccal mucosa, freshly isolated from goat and collected from the slaughterhouse, was soaked for 2 hours in a phosphate buffer (pH 7). The isolated mucosa was then stretched around one end of a double-end open glass tube, making the effective surface area of the membrane equal to 3.14 cm 2 diameter.…”