Preparation of orodispersible tablets of bosentan using xylitol and menthol as dissolution enhancers.

Bosentan is a drug used to treat pulmonary hypertension via dual endothelial receptor antagonism. Bosentan has a restricted oral bioavailability, a problem that's mostly due to poor solubility and hepatic metabolism. It is extensively used for the elderly and children who require a friendly dosage form like orodispersible tablets. So, the goal of this research work was to hasten the dissolution rate of bosentan to produce an orodispersible tablet with immediate drug release. Bosentan was exposed to ethanol-assisted kneading with a rise of xylitol or menthol concentrations (1:1 and 1:2 molar ratio of bosentan with excipient). In addition to observing the dissolution behavior, the resulting dry products were investigated using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). The FTIR reflected possible hydrogen bonding with xylitol and menthol. DSC studies reflected a reduction in the enthalpy and Tm. These results with XRD data reflected partial co-amorphization in the case of xylitol and eutaxia in the case of menthol. These modifications were related to an accelerated dissolving rate. The developed systems were fabricated as orodispersible tablets which exhibited immediate release of bosentan. Thus, the current study offered simple co-processing for the preparation of orodispersible bosentan tablets.

Efficacy of prostaglandin E2 versus prostaglandin F2 alpha assisted with narrowband-UVB in stable vitiligo.

In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.

Topical Oxybutynin 3% Gel Versus Aluminum Chloride 15% Lotion in Treatment of Primary Focal Hyperhidrosis.

INTRODUCTION: Hyperhidrosis is excessive sweating beyond thermoregulatory needs. It is a potentially disabling condition with challenging management. Aluminum chloride is the established topical treatment; however, response remains unsatisfactory. Oxybutynin is an anticholinergic drug that stands as a therapeutic chance for hyperhidrosis. OBJECTIVES: comparing the efficacy of topical oxybutynin 3% gel versus aluminum chloride 15% lotion in treatment of primary focal hyperhidrosis. METHODS: Forty patients with hyperhidrosis were randomly distributed into 2 equal groups treated by either topical oxybutynin 3% gel or topical aluminum chloride 15% lotion once daily night application for 4 weeks (both groups). Evaluation was done at 2 and 4 weeks of treatment and after 1 month of the end of treatment for follow up by Minor iodine starch test, hyperhidrosis disease severity scale (HDSS) and dermatology life quality index (DLQI). RESULTS: Both treatment modalities were effective with insignificant differences between patients of both groups regarding improvement in Minor iodine starch test and HDSS after 2 weeks of treatment (P = 0.561, 0.33 respectively). Oxybutynin 3% gel yielded significantly better improvement of Minor's test, HDSS and patient's quality of life at the end of 4 weeks of treatment with lower recurrence rate than aluminum chloride 15% lotion at 1 month follow up. Minimal adverse effects were noted in both studied groups. CONCLUSIONS: Oxybutynin 3% gel could be considered as a promising treatment modality for hyperhidrosis with higher efficacy than aluminum chloride 15% lotion and lower recurrence rate.

Effect of neat and binary vehicle systems on the solubility and cutaneous delivery of piperine.

Vitiligo is a skin disease characterized by depigmentation disorders due to lack of melanin production. Piperine, an alkaloid extracted from black piper, is active in melanocytes proliferation. To achieve this, the drug has to reach the melanocytes which exist in the deep layer of the epidermis. Higher drug concentration can be obtained after application of optimized formulation to skin. Accordingly, the aim of this work is to investigate the effect of vehicles on skin penetration of piperine as the first step in development of optimized formulation. The tested vehicles include ethanol (Eth), propylene glycol (PG), polyethylene glycol 400 (PEG), and oleic acid (OA) and their combinations. Water was used as the control and skin permeation was monitored using rabbit ear model skin. The highest piperine solubility (48.6 mg/ml) and flux (40.8 µg/cm2 h) was achieved by Eth and the lowest piperine flux (1.17 µg/cm2 h) was reported for PEG. PG and OA showed piperine flux values comparable to that of the control. Among different combination systems, Eth-OA (75:25) binary system had the highest piperine flux (59.3 µg/cm2 h) followed by Eth-OA (50:50) (32.3 µg/cm2 h) and PG-OA (90:10) (22.7 µg/cm2 h). The study thus introduced a vehicle system as the first step in the development of topical formulation of piperine.

Efficacy of topical latanoprost versus minoxidil and betamethasone valerate on the treatment of alopecia areata.

BACKGROUND: Alopecia areata (AA) is one of the most common causes of localized hair loss. There is no universally proven therapy that induces and sustains remission of hair growth in AA. OBJECTIVE: To compare the efficacy and safety of topical latanoprost, minoxidil and betamethasone valerate on hair growth in patients with AA. PATIENTS AND METHODS: Hundred patients with AA classified into five groups of 20 treated with: Group I, latanoprost 0.1% lotion; Group II, minoxidil 5% lotion; Group III, betamethasone valerate 0.1% solution; Group IV, combination of latanoprost lotion and betamethasone valerate solution and Group V, a vehicle lotion control group. RESULTS: There was a statistically significant improvement in all therapeutic groups when compared with control group and reduction of severity of alopecia tool score of scalp and beard before and after treatment for all therapeutic groups. CONCLUSION: Latanoprost, minoxidil and betamethasone valerate are effective and safe in the treatment of patchy AA. The use of latanoprost added to the therapeutic efficacy of topical betamethasone valerate in the treatment of AA and could be an effective adjunctive topical therapy for AA.

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100.

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels.

Effect of binary and ternary solid dispersions on the in vitro dissolution and in-situ rabbit intestinal absorption of gliclazide.

Solid dispersion technique is widely used to improve the dissolution rate of drugs. Most investigators relied on the in-vitro characterization and considered the enhanced dissolution as an indication of improved bioavailability. The current study investigated the effects of binary and ternary solid dispersions of gliclazide with polyethylene glycol 6000 (PEG 6000) and/or pluronic F68 (PL F68) on the dissolution of gliclazide. The study also investigated the intestinal absorption in presence of solid dispersion components. The latter employed the in-situ rabbit intestinal perfusion technique. Preparation of binary solid dispersion with PEG 6000 or PL F68 significantly enhanced the dissolution rate compared to pure drug. The ternary solid dispersion of gliclazide with both polymers resulted in rapid drug dissolution with most drug being released in the first five minutes. The intestinal perfusion indicated the possibility of complete drug absorption from the small intestine. This, together with slow dissolution of pure drug suggested that the absorption of gliclazide is dissolution rate limited. The presence of PEG 6000 did not alter the intestinal absorption but PL F68 showed a trend of enhanced intestinal absorption of the drug. Ternary solid dispersion can thus provide rapid absorption due to rapid dissolution and potential increase in intestinal permeability.