Fungal infections of the skin are one of the often faced with dermatological diseases in worldwide. Topical therapy is an attractive choice for the treatment of the cutaneous infections due to its advantageous such as targeting of drugs to the site of infection and reduction of the risk of systemic side effects. Currently, antifungal drugs are generally used as conventional cream and gel preparations in topical treatment. The efficiency of that treatment depends on the penetration of drugs through the target layers of the skin at the effective concentrations. However, stratum corneum, the outermost layer of the skin, is an effective barrier for penetration of drugs into deeper layers of the skin. The physicochemical characteristics of drug molecules and the types of the formulations are effective factors in topical drug delivery. Therefore, a number of formulation strategies have been investigated for delivering antifungal compounds through targeted site of the skin. This review article focuses on the new alternative formulation approaches to improve skin penetration of antifungal drugs.

Chitosan-based carriers have important potential applications for the administration of drugs. In the present study, topical gel formulations of terbinafine hydrochloride (T-HCl) were prepared using different types of chitosan at different molecular weight, and the antifungal inhibitory activity was evaluated to suggest an effective formulation for the treatment of fungal infections. The characteristics of gel formulations were determined with viscosity measurements and texture profile analysis. Stability studies were performed at different temperatures during 3 months. The ex vivo permeation properties were studied through rat skin by using Franz diffusion cells. The antifungal inhibitory activity of formulations on Candida species and filamentous fungi was also examined with agar-cup method. The microbiological assay was found suitable for determination of in vitro antifungal activity of T-HCl. A marketed product was used to compare the results. The antifungal activity of T-HCl significantly increased when it was introduced into the chitosan gels. A higher drug release and the highest zone of inhibition were obtained from gels prepared with the lowest molecular weight chitosan (Protasan UP CL 213) compared to that of other chitosan gels and marketed product. These results indicated the advantages of the suggested formulations for topical antifungal therapy against Candida species and filamentous fungi.

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Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

The publication of the International Conference of Harmonization (ICH) Q8, Q9, and Q10 guidelines paved the way for the standardization of quality after the Food and Drug Administration issued current Good Manufacturing Practices guidelines in 2003. "Quality by Design", mentioned in the ICH Q8 guideline, offers a better scientific understanding of critical process and product qualities using knowledge obtained during the life cycle of a product. In this scope, the "knowledge space" is a summary of all process knowledge obtained during product development, and the "design space" is the area in which a product can be manufactured within acceptable limits. To create the spaces, artificial neural networks (ANNs) can be used to emphasize the multidimensional interactions of input variables and to closely bind these variables to a design space. This helps guide the experimental design process to include interactions among the input variables, along with modeling and optimization of pharmaceutical formulations. The objective of this study was to develop an integrated multivariate approach to obtain a quality product based on an understanding of the cause-effect relationships between formulation ingredients and product properties with ANNs and genetic programming on the ramipril tablets prepared by the direct compression method. In this study, the data are generated through the systematic application of the design of experiments (DoE) principles and optimization studies using artificial neural networks and neurofuzzy logic programs.

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