Enhanced Loading Efficiency and Mucoadhesion Properties of Gellan Gum Thin Films by Complexation with Hydroxypropyl-β-Cyclodextrin.

Alessandra Adrover,Chiara Brandelli,Laura Di Muzio,Jordan Trilli,Patrizia Paolicelli,Stefania Petralito,Maria Antonietta Casadei

doi:10.3390/pharmaceutics12090819

Alessandra Adrover, Chiara Brandelli + Show 5 more

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https://doi.org/10.3390/pharmaceutics12090819

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Journal: Pharmaceutics	Publication Date: Aug 28, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Sapienza University of Rome

Abstract

Polymeric oral thin films (OTFs) were prepared by the casting method, combining gellan gum (GG), a water-soluble polysaccharide, and glycerol (Gly) as a plasticizing agent. GG-Gly films were investigated as potential systems for buccal drug delivery using fluconazole (Class I of the Biopharmaceutical Classification System) as a model drug. At a low concentration of Gly drug precipitation occurred while, for higher concentrations of Gly, a significant deterioration of mucoadhesive and mechanical properties was observed. One possible way to overcome all these problems could be the addition of hydroxypropyl--cyclodextrin (HP--CD) to the GG-Gly formulation as a drug-precipitation inhibitor. In this work the effect of cyclodextrin addition on the mechanical, mucoadhesive, swelling and release properties of GG-Gly films was investigated. In-vitro drug release studies were carried out using the paddle type dissolution apparatus (USP II) and the millifluidic flow-through device (MFTD). A moving-boundary model for swelling dynamics and release in USP II is proposed to estimate the effective diffusivity of the solvent, HP--CD, fluconazole and complex fluconazole/HP--CD in the swelling film. Experimental results, supported by theoretical modeling, confirmed that gellan gum-low glycerol thin films including HP--CD represent a suitable formulation for fluconazole drug delivery. A sustained release was observed when GG-Gly film is loaded with a preformed complex fluconazole/HP--CD.

Highlights

The oral dosage form for GI-tract delivery represents the preferred way for drug administration as it is the most convenient, practical and accessible way for the assumption of biological active agents
Experimental results, supported by theoretical modeling, confirmed that gellan gum-low glycerol thin films including HP-β-CD represent a suitable formulation for fluconazole drug delivery
It was observed that the gelation temperature slightly shifted from 50 to 52 ◦C when glycerol was added to gellan gum (GG) solutions, from 0.5% to 6% w/v

Summary

Introduction

The oral dosage form for GI-tract delivery represents the preferred way for drug administration as it is the most convenient, practical and accessible way for the assumption of biological active agents. The oral mucosa has been identified as an interesting option for the administration of bioactive molecules [3] It is accessible and offers ease of application of pharmaceutical dosage forms, and their prompt removal in case of need [4]. Oral mucosa presents a relatively low enzyme activity, enabling the preservation of labile drugs from degradation and it can be used to obtain both local and systemic therapeutic effects. In the latter case, a therapeutic molecule can directly access the systemic circulation through the internal jugular vein, avoiding first-pass hepatic metabolism, and reaching high plasma concentrations [4]. All these advantages stimulated the design of innovative buccal dosage forms such as oral thin films (OTFs) that attracted increasing attention and attained a preeminent position over other formulations

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