Mucoadhesive Wafers Research Articles

Synthesis of Methacryloylated Hydroxyethylcellulose and Development of Mucoadhesive Wafers for Buccal Drug Delivery

Non-ionic hydroxyethylcellulose (HEC) has limited mucoadhesive properties for application in transmucosal drug delivery. In this study, HEC was chemically modified by reaction with glycidyl methacrylate. This allowed introducing the methacryloyl groups to HEC structure to make it capable of forming covalent bonds with the sulfhydryl groups present in the mucin glycoprotein to achieve enhanced mucoadhesive properties. The results showed a successful modification of HEC as confirmed by 1H NMR and FTIR spectroscopies. The quantification of methacryloyl moieties was conducted using HPLC. The toxicity studies using in vivo planaria acute toxicity assay, in vivo planaria fluorescent test, and in vitro MTT assay with Caco-2 cell line confirmed that the chemical modification of HEC does not result in any toxicological effects. Mucoadhesive wafers were developed based on parent and modified HEC as a model dosage form for buccal delivery. The mucoadhesive properties of modified HEC assessed using a tensile test were found to be significantly better compared to unmodified HEC.

Water-soluble chitosan eases development of mucoadhesive buccal films and wafers for children

Oromucosal films and wafers are user-friendly solid dosage forms offering easy and convenient administration, as well as rapid or controlled drug delivery. The aim of this study was to develop prednisolone containing child-friendly chitosan-based mucoadhesive films and wafers with a prolonged residence time on the buccal mucosa. Four different chitosan types (different molecular weights, degree of deacetylation (DDA), pattern of deacetylation) were studied for films prepared by solvent-cast-evaporation and wafers by freeze-drying. Mucoadhesive properties correlated with swelling abilities and were dependent on the chitosan type, the solvent, and the preparation method. Mucoadhesive forces were higher for formulations containing chitosan with higher DDA and for wafers compared to films. The drug release was relatively fast, especially for films (approx. 90 % in 15 minutes) and steadier for wafers (90 % in 45–120 minutes). Permeability was evaluated using artificial membranes and HT29-MTX cell-monolayers. The developed formulations exhibited good biocompatibility. Organoleptic properties can be improved by choosing a homogenously deacetylated chitosan type that provides a more neutral pH. Using hydroxypropyl-beta-cyclodextrin-complexation for taste masking of bitter drugs also reduced wafers’ drug release rate. Mucoadhesive wafers are promising alternatives to films with a slower drug release rate and stronger mucoadhesion.

Novel Mucoadhesive Wafers for Treating Local Vaginal Infections.

Current vaginal formulations, such as gels and pessaries, have limitations, including poor retention. Therefore, the use of mucoadhesive formulations that adhere to the vaginal wall would allow prolonged retention and controlled drug release while reducing the required dose and the potential toxicity associated with high drug loading. The aim of the current research was to develop, characterize, and optimize freeze-dried wafers loaded with metronidazole (MTz) to treat vaginal bacterial infections. Blank (BLK) composite wafers comprising carrageenan (CARR) and sodium alginate (SA) were initially formulated; however, due to poor physico-chemical properties, Carbopol (CARB), hydroxypropylmethylcellulose (HPMC), and polyethylene glycol 200 (PEG) were included. The MTz-loaded formulations were obtained by loading optimized composite CARB:CARR- or CARB:SA-based gels (modified with HPMC and/or PEG) with 0.75% of MTz prior to freeze-drying. The physico-chemical properties were investigated using texture analysis (resistance to compressive deformation and adhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Functional properties were investigated by examining the swelling, porosity, drug release, and in vitro antimicrobial activity using E. coli as a model infection-causative agent. The results showed that HPMC and PEG generally improved the wafer's appearance, with smoother surfaces for easy insertion. From the physico-chemical characterization studies, only two composite wafers prepared from 8% CARB:SA 1:4 and 8% CARB:SA 1:9 gels were deemed optimal and loaded with MTz. Both formulations showed sustained drug release and achieved almost 100% cumulative release within 72 h in simulated vaginal fluid. The data obtained from the drug dissolution (release) experiments were fitted to various mathematical equations and showed the highest correlation coefficient with the Higuchi equation, suggesting a drug release based on diffusion from a swollen matrix; this was confirmed by the Korsmeyer-Peppas equation. The released MTz inhibited the growth of the E. coli used as a model bacterial organism.

Preparation and characterization of benzydamine hydrochloride-loaded lyophilized mucoadhesive wafers for the treatment of oral mucositis

Chemo/radiotherapy-induced oral mucositis (OM) has painful ulcers that can impair patients' lives. This study aimed to develop and characterize (in vitro and in vivo) benzydamine (BNZ) freeze-dried mucoadhesive wafers from chitosan (CS) in combination with different hydrophilic polymers as a locally controlled delivery system for OM treatment. The porous (69–83%) optimum wafers (0.02–0.03 g and 3.2–4.3 mm) released 90–95% of their drug content over 8 h and demonstrated 40–53 g mucoadhesion strength. Mechanical evaluations of F1 (CS) and F14 (CS/HPMC (3:1)) selected formulations showed modulus of elasticity, tensile strength, and % elongation at break ranging from 0.2 to 0.3 MPa, 0.01–0.02 MPa, and 15–18%, respectively. The antimicrobial efficacy of BNZ-loaded wafers was significantly higher than drug-free ones. The extract solutions of the drug-free and BNZ-loaded wafers revealed 100 and 20% viability in human gingival fibroblasts (HGFs) exposure. In vivo analysis demonstrated that BNZ-loaded wafers represented a significant reduction in macroscopic evaluation of OM and histopathological tests compared to positive and negative controls and drug-free wafers. Conclusively, lyophilized F1 and F14 mucoadhesive wafers had acceptable structural, mechanical, and biological properties and might be promising drug delivery systems for OM.

Preparation and Characterization of Benzydamine Hydrochloride-Loaded Lyophilized Mucoadhesive Wafers for the Treatment of Oral Mucositis

Preparation and Characterization of Benzydamine Hydrochloride-Loaded Lyophilized Mucoadhesive Wafers for the Treatment of Oral Mucositis

Mucoadhesive wafers composed of binary polymer blends for sublingual delivery and preservation of protein vaccines

The objective of this study is to develop a simple biopolymer platform of mucoadhesive wafers that enables effective sublingual delivery and preservation of protein vaccines. The wafers were composed of a series of binary polymer blends of carboxymethylcellulose (CMC) and alginate (ALG). Varying the ratio between CMC and ALG resulted in wafers with different microstructure, mechanical properties, disintegration time, and release kinetics of model compounds. Wafers with high CMC content were highly mucoadhesive to sublingual mucosal tissue and could withstand extensive washing, leading to improved protein permeation into the tissue. On the other hand, wafers with high ALG content were not only mechanically robust, but also able to protect a model enzyme (β-galactosidase) against lyophilization and heat challenge. HIV gp140 protein loaded in wafers of the optimal composition could be stored and transported without cold chain, while maintaining antigen-specific immunogenicity after sublingual vaccination in mice. These findings established that the CMC/ALG binary blend polymer wafers have the potential to improve the sublingual delivery and storage stability of protein-based vaccines.

Mucoadhesive wafers for buccal delivery of probiotic bacteria: Mechanical properties and enumeration

The development of probiotic formulations has attracted great attention of researchers and industrial community. Their beneficial effects have been demonstrated in human health, and in buccal cavity including prevention of gingivitis, periodontitis, dental caries, oral candidiasis, and immunomodulation. The development of mucoadhesive wafers as buccal systems is important to promote intimate contact between the probiotics and oral mucosa, as well as maintain the viability of anaerobic bacteria like Bifidobacterium bifidum BB12. The aim of this study was to develop wafers systems containing poloxamer 407, Carbopol 974 P®, probiotic microorganisms Bifidobacterium bifidum BB12 for oral cavity administration. Two concentrations of microorganisms were incorporated to the polymer blends and freeze-dried. The morphological, enumeration of bacteria and mechanical properties of the wafers with and without probiotic bacteria were examined. The most concentrated formulation demonstrated more difficulties in freeze-drying process and lower enumeration of B. bacterium BB12. The wafers containing probiotic microorganisms (1:10) could be stored during 14 days with probiotic benefits. Their mechanical properties were suitable, because of improved cohesiveness, adhesion properties and firmness in comparison to formulations without probiotics. The wafers were suitable to carry probiotic microorganisms for 14 days and suitable mechanical properties for buccal application.

Microemulsion-Based Mucoadhesive Buccal Wafers: Wafer Formation, In Vitro Release, and Ex Vivo Evaluation.

Microemulsion has the potentials to enhance dissolution as well as facilitate absorption and permeation of poorly water-soluble drugs through biological membranes. However, its application to govern a controlled release buccal delivery for local treatment has not been discovered. The aim of this study is to develop microemulsion-based mucoadhesive wafers for buccal delivery based on an incorporation of the microemulsion with mucoadhesive agents and mannitol. Ratio of oil to surfactant to water in the microemulsion significantly impacted quality of the wafers. Furthermore, the combination of carbopol and mannitol played a key role in forming the desired buccal wafers. The addition of an extra 50% of water to the formulation was suitable for wafer formation by freeze-drying, which affected the appearance and distribution of carbopol in the wafers. The amount of carbopol was critical for the enhancement of mucoadhesive properties and the sustained drug release patterns. Release study presented a significant improvement of the drug release profile following sustained release for 6h. Ex vivo mucoadhesive studies provided decisive evidence to the increased retention time of wafers along with the increased carbopol content. The success of this study indicates an encouraging strategy to formulate a controlled drug delivery system by incorporating microemulsions into mucoadhesive wafers.

Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs

Lyophilized muco-adhesive wafers with optimum drug loading for potential buccal delivery have been developed. A freeze-annealing cycle was used to obtain optimized wafers from aqueous gels containing 2% κ-carrageenan (CAR 911), 4% pluronic acid (F127), 4.4% (w/w) polyethylene glycol with 1.8% (w/w) paracetamol or 0.8% (w/w) ibuprofen. Thermogravimetric analysis showed acceptable water content between 0.9 and 1.5%. Differential scanning calorimetry and X-ray diffraction showed amorphous conversion for both drugs. Texture analysis showed ideal mechanical and mucoadhesion characteristics whilst both drugs remained stable over 6 months and drug dissolution at a salivary pH showed gradual release within 2h. The results show the potential of CAR 911 and F127 based wafers for buccal mucosa drug delivery.