Stefan Bouckaert

In-vitro Bioadhesion of a Buccal, Miconazole Slow-release Tablet

Abstract— The bioadhesive characteristics of thermally modified starch/polyacrylic acid (PAA) tablets, containing miconazole nitrate, were determined. The detachment force and work of adhesion were significantly affected by the ratio of drum‐dried waxy maize starch and PAA. Pure PAA showed the highest detachment force and work of adhesion while the lowest force and work of adhesion were observed for pure starch. There was a pronounced effect of molecular weight of PAA on the bioadhesive characteristics. Miconazole nitrate did not influence bioadhesion up to a concentration of 30%. The influence of additives was negligible and fluctuations of pH did not influence the bioadhesive strength of the tablet.

Comparison of salivary miconazole concentrations after administration of a bioadhesive slow-release buccal tablet and an oral gel.

SummaryThe salivary miconazole concentrations after administration of a bioadhesive slow-release buccal tablet and an oral gel have been compared. The bioadhesive tablet consisted of a mixture of thermally modified starch and 5% polyacrylic acid.Although the amount of drug administered via the bioadhesive tablet was sixfold lower than when the gel was used, the salivary miconazole levels were higher and remained above the MIC value ofCandida albicans for more than 10 hours. The mean adhesion time of the tablet was 586 min.The bioadhesive tablet appears to be a promising drug delivery system for the buccal administration of drugs for local therapy.

Deterioration of the Provox(TM) silicone tracheoesophageal voice prosthesis: Microbial aspects and structural changes

Device life of tracheoesophageal voice prostheses is limited due to deterioration of the polymers. A group of 55 postlaryngectomy patients fitted with a Provox voice prosthesis have been studied prospectively during 6 months. Thirty-seven prostheses were replaced due to a dysfunctional valve mechanism. Although colonization with Candida species was highly associated with destruction of the silicone material, other upper respiratory tract commensals, e.g. Staphylococcus aureus, were also demonstrated. Electron microscopy of the contaminated devices showed colonization and disruption of the silicone material by penetrating yeast hyphae. During the study a remarkable increase of intratracheal phonatory pressures was assessed with progressive colonization of the prostheses.

Enhancement of dissolution rate of nifedipine using sucrose ester coprecipitates

Abstract The dissolution rate enhancement properties of sucrose esters were evaluated. Coprecipitates of nifedipine with different sucrose esters were prepared and drug dissolution and the stability of drug dissolution were studied. The use of sucrose palmitate of high HLB value dramatically improved the dissolution rate, especially when a drug/ester ratio of 1 : 14 was used. Increasing the drug/ester ratio produced a more amorphous product, progressively increasing the dissolution rate. Although the results are promising, the use of sucrose esters is probably very much restricted due to their hydrolytic instability during storage and the progressively increasing crystallinity of the coprecipitate.

Preliminary efficacy study of a bioadhesive vaginal metronidazole tablet in the treatment of bacterial vaginosis.

Bacterial vaginosis is a common cause of vaginitis, characterized by replacement of lactobacilli-dominated fluor with a mixed flora containing Gardnerella vaginalis, various anaerobic bacteria and Mycoplasma hominis. Metronidazole is the drug of choice in the treatment of bacterial vaginosis, but dosage and duration of therapy are still controversial. The current recommendation is a treatment with metronidazole orally with 500mg twice daily for seven days (Centers for Disease Control 1989), but a 2-g single-dose oral metronidazole regimen has been shown to be as effective (Lugo-Miro et a1 1992). However, metronidazole has some unpleasant side-effects and is contraindicated in the first trimester of pregnancy. Alternative therapy has been sought as a clindamycin vaginal cream (Schmitt et a1 1992). Recently, an increasing interest in the development of vaginal bioadhesive tablets has been shown because of the advantages of maintaining a certain drug level locally and enabling lower dosing frequency and a lower amount of drug administered (Brannon-Peppas 1993). This study has been designed to evaluate the efficacy of a single vaginal metronidazole bioadhesive tablet application vs a standardized oral treatment with metronidazole. The bioadhesive formula has already succesfully been used as a buccal bioadhesive tablet containing miconazole nitrate to treat candidiasis (Bouckaert et a1 1992). In a double-blind study the patients were randomly allocated to receive a bioadhesive vaginal tablet (weight 1 g; diam. 20 mm) with 100 mg metronidazole or a placebo vaginal tablet. The bioadhesive matrix consisted of a modified starch/polyacrylic acid mixture (Bottenberg et al 1991). Both groups were compared with a third arm of the study where patients were given the conventional oral metronidazole treatment consisting of two 500-mg doses daily of Flagyl over seven days. In the case of treatment with the bioadhesive tablet, a single tablet was applied to the cervix at the out-patient clinic. The bioadhesive tablet was fixed on the portio uteri previously cleaned with a dry tamp. The tablet was applied with tweezers or forceps. Patients were asked to record the loss of a tablet. The patient’s complaints,

Optimization of a Granulation Procedure for a Hydrophilic Matrix Tablet Using Experimental Design

An experimental design was used in order to optimize a granulation procedure in a high-shear mixer for a hydrophilic matrix tablet formulation. The parameters tested were the amount of water in the hydroalcoholic granulation liquid, the amount of granulation liquid, and the massing time. The amount of granulation liquid was the most important parameter, followed by the amount of water in the granulation liquid. The influence of the massing time was negligible. A granule with a friability below 20% was obtained.

Influence of the buccal application site of a bioadhesive slow-release tablet on salivary miconazole concentrations in irradiated patients

Cancer patients, irradiated in the neck region, often develop oral candidosis and a substantial decrease in salivary flow after irradiation. As the use of a bioadhesive buccal tablet containing miconazole nitrate has been shown to be effective in the treatment of oral candidosis, the influence of the application site on the buccal levels of miconazole nitrate was studied. The tMAX the adhesion time and T>MIC were significantly higher (P < 0.05) when the gingiva was chosen as the application site in comparison with the cheek. The CMAX, tMAX and AUC were not significantly different. The gingiva is the application site of choice in irradiated patients even with a decreased salivary flow.