Scale up of Semisolid Dosage Forms Manufacturing Based on Process Understanding: from Lab to Industrial Scale.

The scale up of production processes is a major challenge in pharmaceutical industry. Using a quality by design approach, upscaling can be based on the design space, which can be assessed on a small scale. In a previous study, the critical process parameters were identified by a definitive screening design on cetomacrogol ointment. In the current study, this lab scale (0.5 kg) study was scaled up to industrial scale (2000 kg, filling 100g tubes at 75 tubes/min). A similar trend for the influence of filling temperature on ointment yield stress was found for lab and industrial scale production. Furthermore, a process window for ointment filling viscosities was established. It was shown that between 26 and 170 Pa.s ointment could be filled into tubes with a low weight variation (< 0.5% RSD) resulting in a product with a yield stress that meets the pre-set criteria. This approach was subsequently verified using several creams and ointments and showed general applicability.

Liquid Crystal Formulation and Optimization of Anti-Microbial Polyherbal Ointment.

We examined the formulation of liquid crystalline systems (LCS) including 5% TSE extracts and analyzed marker substances of the 5% TSE ointment by HPLC-DAD. The TSE extracts were evaluated for its anti-bacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. We found the extracts showed predominant activity against selected bacterial species. The result of the polarized light microscopy, differential scanning calorimetry (DSC), small-angle X-ray diffraction (SXRD), and rheology analysis indicated the presence of LCS structures with lamellar arrangement. DSC of the TSE formulas showed higher transition peak temperature at 60 °c for the phase. SXRD observation of the LCS formulas showed that the structures of the LCS formulas were in the lamellar liquid crystalline phase. Further, to ensure the quality and purity of the TSE ointment, HPLC analysis was performed by measuring the. content of 2 marker substances. The contents of marker substances in the TSE ointment were calculated as 0.078% (paeoniflorin) and 0.031% (glycyrrhizin), respectively. Taken altogether, our study report successful generation of LCS made of 5% TSE ointment and its antimicrobial activity. Moreover, the quantitation of the two active components enable a proper quality control of the TSE extracts, that is essential for the development of ointment products.

Optimization of topical gels with betamethasone dipropionate: selection of gel forming and optimal cosolvent system.

The purpose of these studies was to develop a 0.05% betamethasone gel characterized by physical-chemical stability and good release properties. The preliminary studies were designed to select the gel-forming agents and the excipients compatible with betamethasone dipropionate. In order to formulate a clear gel without particles of drug substances in suspension, a solvent system for the drug substance was selected. The content of drug substance released, the rheological and in vitro release tests were the tools used for the optimal formulation selection. A stable carbomer gel was obtained by solubilization of betamethasone dipropionate in a vehicle composed by 40% PEG 400, 10% ethanol and 5% Transcutol.

Formulation of creams with betamethasone dipropionate: evaluation of chemical stability.

The aim of this study was to investigate how the different excipients influenced the chemical stability of betamethasone dipropionate in creams. The chemical stability was evaluated by analyzing betamethasone related substance content. Transcutol is the excipient ensuring maximum stability to betamethasone. Incompatibilities between betamethasone dipropionate and hexylene glycol were observed. The pH values in the weak acid range confer chemical stability to betamethasone.

Dexamucobase: a novel treatment for oral aphthous ulceration.

OBJECTIVES: Recurrent oral aphthous ulceration is a common condition treated with topical anti-inflammatory drugs, such as triamcinolone acetonide in Orabase (Kenalog in Orabase, Bristol-Myers Squibb). The aim of the study was to synthesize a novel dental paste containing dexamethasone and assess the therapeutic effect of this paste in comparison with a commonly used treatment, triamcinolone acetonide in Orabase, in oral aphthous ulceration. METHOD AND MATERIALS: The design was a case-control study. The setting was the laboratory of postgraduate students in the College of Pharmacy, University of Mosul, Iraq. Clinical evaluation of the paste was conducted in the outpatient clinic of the Oral Medicine Department, College of Dentistry, University of Baghdad, Iraq. The novel paste (named dexamucobase) was prepared under aseptic conditions and evaluated for its therapeutic effect in 53 patients with recurrent aphthous stomatitis, in comparison with 37 patients treated with triamcinolone acetonide in Orabase. RESULTS: Healing of the ulcer was significantly faster (P < .001), and adverse effects were significantly reduced (P < .01) for the dexamucobase treatment compared to Kenalog in Orabase. There was no significant difference in the speed of pain reduction between the dexamucobase treatment compared to Kenalog in Orabase. CONCLUSIONS: The novel dexamucobase was found to be equally effective in treating oral aphthous ulceration, with some advantages, as the widely used preparation Kenalog in Orabase.

Anionic clays for sunscreen agent safe use: photoprotection, photostability and prevention of their skin penetration.

The use of sunscreen preparations is recently growing and their efficacy and safety must be taken into account since they are applied on the skin frequently and for many hours. Exposition to sunlight, in fact, can cause sunscreen photodegradation and determine their decrease in UV protection often with the occurrence of allergic and/or toxic degradation products. A high photostability is hence very important for their effectiveness and safety. The aim of this work is to obtain new sunscreen formulations stabilized by intercalating PABA, within the lamellar structures of two kinds of hydrotalcite. PABA was chosen as model sunscreen because of its high photoinstability and photosensitizing properties that nowadays bar its utilization. Both intercalated products showed an increased protection range and, in one case, an improved sunscreen photostability. Sunscreen release from creams containing intercalated or free PABA was evaluated as well. The very low or negligible sunscreen release, obtained from the intercalated product loaded formulations, resulted in a lack of a close contact between skin and filter with the consequence that cutaneous reactions and allergy problems are eliminated. The use of these materials resulted in a good strategic technological approach in order to increase efficacy and safety of solar products.

The effect of preprocessing methods in reducing interfering variability from near-infrared measurements of creams.

This work is part of a study in which the possibility of NIR combined with some chemometrical methods is investigated as a suitable technique to classify clinical study samples of a cream. In this study, the influence of different preprocessing methods on the removal of spectral variations due to some variance sources has been investigated. The applied preprocessing methods are standard normal variate (SNV), detrend correction, offset correction, and first and second derivation. The investigated variance sources are different batches of ingredients, different samples of the same batch, different days and different positions of the sample cup in the sample drawer of the instrument. A nested ANOVA design has been applied in order to quantify the variances introduced by these variance sources. Since ANOVA is a univariate technique, the necessary variable (wavelength) selection has been performed by the Fisher criterion. The best results, i.e. largest reduction of interfering variability and clearest distinction between different clinical study samples, are obtained with the second derivative spectra.