Mechanical, optical, and physicochemical properties of HPMC-based doxazosin mesylate orodispersible films

Abstract In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product

Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs.

Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing. Nanoplexes of ciprofloxacin - a BCS Class IV compound - prepared by complexation with dextran sulfate were used as the nanosuspension ink at two different sizes (i.e. ≈265nm and 188nm). Inkjet printing was performed on cellulose substrate at 0.25% (w/v) nanosuspension concentration and 5% (w/v) polyethylene glycol. For both nanoplex sizes, the results indicated that the printed dose could be increased by increasing the number of droplets dispensed. However, exact correlations between the achievable dose and the number of droplets dispensed were not evident, which was likely caused by the spatial non-homogeneity in the nanosuspension concentration. Compared to the larger nanoplex, printed nanodrugs of the smaller nanoplex consistently exhibited higher payload with better batch-to-batch reproducibility (<6%). The maximum achievable payload was equal to ≈2.5µg/cm(2), which was multifold higher than that achieved had inkjet printing of ciprofloxacin solution been performed. Nevertheless, print substrate with higher liquid uptake capacity is needed to increase the payload nearer to the therapeutic dose. Lastly, the drug release and non-cytotoxicity of the printed nanodrug were successfully established in vitro.

Effect of 0.3% Hydroxypropyl Methylcellulose/Dextran Versus 0.18% Sodium Hyaluronate in the Treatment of Ocular Surface Disease in Glaucoma Patients: A Randomized, Double-Blind, and Controlled Study.

PURPOSE: To compare the efficacy and safety of 0.3% hydroxypropyl methylcellulose/dextran (HPMC/dextran) and 0.18% sodium hyaluronate (SH) in the treatment of ocular surface disease in patients using antiglaucoma drugs containing preservatives. METHODS: This was a double-blind, randomized, parallel-group study in 70 glaucoma patients with Ocular Surface Disease Index (OSDI) score greater than 20 points and/or presence of ocular signs. Patients were randomized to receive either preservative-free 0.3% HPMC/dextran (n=35) or preservative-free 0.18% SH (n=35). Treatment was 1 drop in each eye, 4 times a day. Data were collected at baseline, at day 7 and day 28. RESULTS: The groups were homogeneous at baseline. At day 28, both treatments showed significant improvements (P<0.05) in the mean OSDI score, lid skin and lid margin inflammation, conjunctival injection, and expressibility of meibomian glands, corneal staining score, fluorescein tear breakup time (FBUT), and Schirmer I test. However, the mean OSDI score, lid margin inflammation and conjunctival injection showed significant improvements (P<0.05) in the SH group at days 7 and 28, compared to the HPMC/dextran group. FBUT and the Schirmer I test also showed significant improvements (P<0.05) in the SH group compared to the HPMC/dextran group, at day 28. No adverse reactions were observed in either group. CONCLUSIONS: Preservative-free artificial tear, 0.3% HPMC/dextran, and 0.18% SH, caused a significant relief of the ocular surface disease in glaucoma patients. However, 0.18% SH led to a greater improvement in ocular signs and symptoms than 0.3% HPMC/dextran.

Histology of a novel injectable filler (polymethylmethacrylate and cross-linked dextran in hydroxypropyl methylcellulose) in a rat model.

A novel injectable filler of polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose was introduced in the commercial filler market. For soft tissue augmentation, safety and biocompatibility should be evaluated and the stability at the implantation site should be assessed using histologic evaluation. In order to evaluate the biocompatibility of the novel soft tissue filler, PMMA and cross-linked dextran in hydroxypropyl methylcellulose was subdermally injected into the skin of Sprague-Dawley Rats. Histologic evaluation was performed at 13 weeks and 12 months after the injection. Inflammatory cell infiltration, neovascularization, and fibrosis were scored according to defined grading systems. The mean score of the histologic evaluation was 5.7 and 3.9 at 13 weeks and 12 months, respectively. At 12 months after injection, the PMMA and cross-linked dextran in hydroxypropyl methylcellulose appeared to be kept in place through fine fibrous capsules. The mixture of PMMA and cross-linked dextran in hydroxypropyl methylcellulose can be safely applied for soft tissue augmentation with longevity of greater than 12 months.

Safety and efficacy of a novel injectable filler in the treatment of nasolabial folds: polymethylmethacrylate and cross-linked dextran in hydroxypropyl methylcellulose.

Nasolabial folds are a sign of aging and increasing number of people want filler injections in their nasolabial folds to look younger. Various dermal fillers are used for the correction of nasolabial folds. Recently, a novel injectible filler, polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose, was introduced for facial contouring. This study was designed as a six-month, prospective, single-blinded, and open-label study in two centers located in Korea. Nineteen Korean patients received the novel filler injections on both nasolabial folds. At Weeks 4, 12, and 24, the efficacy and safety of the dermal filler were evaluated by blinded-investigators using clinical photographs. The mean Wrinkle Severity Rating Scale revealed significant decrease after dermal filler injections at each study visit. The decreased Wrinkle Severity Rating Scale was maintained for 6 months (p < 0.0001). The Global Aesthetic Improvement score showed an improvement greater than 2 in 95% of the per-proto col population 24 weeks after the injections. All patients (100%) experienced an improvement of their nasolabial folds at Week 24. There were no complications related to the novel filler injection. The novel dermal filler, PMMA, and cross-linked dextran in hydroxylpropyl methylcellulose, can be another safe and effective treatment option in the treatment of nasolabial folds.