PVA-based formulations as a design-technology platform for orally disintegrating film matrices

In the majority of pharmaceutical applications, polymers are employed extensively in a diverse range of pharmaceutical products, serving as indispensable components of contemporary solid oral dosage forms. A comprehensive understanding of the properties of polymers and selection the appropriate methods of characterization is essential for the design and development of novel drug delivery systems and manufacturing processes. Orally disintegrating film (ODF) formulations are considered to be a potential substitute to traditional oral dosage forms and an alternative method of drug administration for children and uncooperative adult patients, including those with swallowing difficulties.

Highlights

• The application of weak non-salt forming lactic acid as a solubilizer enabled the dissolution of poorly water soluble haloperidol (BCS class II) in an aqueous PVA solution.
• Spray-drying enabled production of a homogenous PVA/HAL blend with low API content for hot melt extrusion.
• The effect of different processing methods on the physicochemical and pharmaceutical characteristics of films was investigated. The selection of manufacturing method was found to influence the HAL diffusion.
• The processing-structure–property relationships were evaluated.

A multitude of pharmaceutical formulations with varying mechanical and biopharmaceutical properties have emerged from the modification of the original polymeric bulk. Here we propose different formulation approaches, i.e. solvent casting (SC), 3D printing (3DP), electrospinning (ES), and lyophilization (LP) that enabled us to adjust the disintegration time and the release profile of poorly water soluble haloperidol (HAL, BCS class II) from PVA (polyvinyl alcohol) based polymer films while maintaining similar hydrogel composition. In this study, the solubility of haloperidol in aqueous solution was improved by the addition of lactic acid.

The prepared films were evaluated for their morphology (SEM, micro-CT), physicochemical and biopharmaceutical properties. TMDSC, TGA and PXRD were employed for extensive thermal and structural analysis of fabricated materials and their stability. These results allowed us to establish correlations between preparation technology, structural characteristics and properties of PVA films and to adapt the suitable manufacturing technique of the ODFs to achieve appropriate HAL dissolution behaviour.

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Materials

The different dosage forms were obtained using the same starting material, i.e., PVA (Parteck® MXP, PVA 4–88, Merck, Darmstadt, Germany) hydrogel with incorporated haloperidol (HAL, Sigma-Aldrich, Saint-Luis, MA, USA) with 85 % (w/w) lactic acid aqueous solution (LA, Sigma-Aldrich, Saint-Luis, MA, USA) and, in the case of the 3DP formulation, with sorbitol (Parteck® SI 150, Merck, Darmstadt, Germany) additionally. Methanol HPLC grade (Honeywell, France), formic acid (Sigma-Aldrich, Saint-Luis)

Marta Kozakiewicz-Latała, Aleksandra J. Dyba, Dominik Marciniak, Patrycja Szymczyk-Ziółkowska, Mieczysław Cieszko, Karol P. Nartowski, Maciej Nowak, Bożena Karolewicz, PVA-based formulations as a design-technology platform for orally disintegrating film matrices, International Journal of Pharmaceutics, 2024, 124666, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124666.

Read also our introduction article on 3D Printing here: