Design of freeze-dried Soluplus/polyvinyl alcohol-based film for the oral delivery of an insoluble drug for the pediatric use

Abstract

Spironolactone (SL) is a poorly water-soluble drug. Being poorly soluble affects its dissolution rate which in turn affects its oral bioavailability. This work aimed to prepare freeze-dried SL-Soluplus Õ /polyvinyl alcohol (PVA) oral thin film in an attempt to enhance the drug solubility on one hand and at the same time prepare a solid dosage form convenient for the pediatric use. SL-Soluplus Õ /PVA films were prepared using polyethylene glycol 400 (PEG 400) as a plasticizer applying the solvent-casting technique. The prepared films were evaluated for their thickness, tensile strength, and in vitro dissolution studies. Box-Behnken design (17 runs) was applied to optimize the effects of the formulation variables on the film properties. The optimized film formulation was freeze-dried after casting so as to enhance the drug dissolution. Moreover, the optimized freeze-dried film was re-characterized in vitro and evaluated in vivo in human volunteers to investigate its palatability and satisfaction. The results showed that the optimized formulation composed of 10% polymer concentration containing Soluplus Õ :PVA (0.33:0.66) and plasticized with 30% PEG 400 possessed the highest desirability value (0.836). Freeze-drying of the optimized formulation succeeded to improve SL in vitro dissolution due to the preparation of a more porous film compared to the non-freeze-dried one. In vivo evaluation of the optimized freeze-dried film showed high satisfaction among the participating volunteers concerning the ease of administration and sensation thereafter, where all the film specimens dissolved without the need for water and no film residues remained in the mouth following film dissolution. In conclusion, freeze-dried Soluplus Õ /PVA-based oral thin film proved to be a successful carrier for the oral delivery of insoluble drugs like SL for pediatrics.

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

“…Many studies on orodispersible polymer films have been conducted for various reasons; as enhancing solubility of poorly soluble BCS class II drugs, taste masking of antihistamines, or increasing patient compliance for administration of antidepressant drugs (El-Setouhy & El-Malak, 2010;Preis et al, 2012;Sievens-Figueroa et al, 2012). Optimized formulations of orodispersible polymer films were also studied in the literature using simple methodologies such as solvent casting, hot-melt extrusion, and freeze drying (ElMeshad & El Hagrasy, 2011;Low et al, 2013;Kumria et al, 2016;Shamma & Elkasabgy, 2016). The aim of the current study was to improve the dissolution properties of the poorly watersoluble OL via formation of stable OL co-amorphous dispersions (COADs) from successful solid dispersions with some polycarboxylic acids (CAPs) .…”

Application of freeze-drying in the development of oral drug delivery systems

“…Hence, an increase in concentration of polymers (Carbopol and starch) helped to increase the film tensile strength. In another study, freeze-dried ODFs comprising Soluplus® and PVA as filmforming materials and solubilizing agents showed comparable tensile strength and improved in vitro dissolution profiles compared to the non-freeze-dried film [94].…”

Hot Melt Extrudates Formulated Using Design Space: One Simple Process for Both Palatability and Dissolution Rate Improvement

“…Palatability improvement provided by formulations containing SOL has already been reported before. 33 The taste-masking ability of extrudates could be related to drug dispersion into polymeric matrix and to sample dissolution behavior. Better results of taste masking achieved by HME systems containing SOL could be explained by the capacity of this polymer to form micelles, in which the drug is isolated inside the structure, less available to activate electric potential in Astree e-tongue.…”