Pharmaceutical Statistics: Practical and Clinical Applications

Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs). These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API) within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

Orally disintegrating films: A modern expansion in drug delivery system.

Transdermal drug delivery systems are a constant source of interest because of the benefits that they afford in overcoming many drawbacks associated with other modes of drug delivery (i.e. oral, intravenous). Because of the impermeable nature of the skin, designing a suitable drug delivery vehicle that penetrates the skin barrier is challenging. Gels are semisolid formulations, which have an external solvent phase, may be hydrophobic or hydrophilic in nature, and are immobilized within the spaces of a three-dimensional network structure. Gels have a broad range of applications in food, cosmetics, biotechnology, pharmatechnology, etc. Typically, gels can be distinguished according to the nature of the liquid phase, for example, organogels (oleogels) contain an organic solvent, and hydrogels contain water. Recent studies have reported other types of gels for dermal drug application, such as proniosomal gels, emulgels, bigels and aerogels. This review aims to introduce the latest trends in transdermal drug delivery via traditional hydrogels and organogels and to provide insight into the latest gel types (proniosomal gels, emulgels, bigels and aerogels) as well as recent technologies for topical and transdermal drug delivery.

Recent advances in gel technologies for topical and transdermal drug delivery

Lipid based nanocarriers: a translational perspective

Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: in vitro/in vivo evaluation.

The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion-based gel of terbinafine for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the amount of oil (X
 1), Smix (mixture of surfactant and cosurfactant; X
 2) and water (X
 3) in the microemulsion. The formulations were assessed for globule size (in nanometers; Y
 1) and solubility of drug in microemulsion (in milligrams per milliliter; Y
 2). The microemulsion containing 5.75% oil, 53.75% surfactant–cosurfactant mixture and 40.5% water was selected as the optimized batch. The globule size and solubility of the optimized batch were 18.14 nm and 43.71 mg/ml, respectively. Transmission electron microscopy showed that globules were spherical in shape. Drug containing microemulsion was converted into gel employing 0.75% w/w carbopol 934P. The optimized gel showed better penetration and retention in the human cadaver skin as compared to the commercial cream. The cumulative amount of terbinafine permeated after 12 h was 244.65 ± 18.43 μg cm−2 which was three times more than the selected commercial cream. Terbinafine microemulsion in the gel form showed better activity against Candida albicans and Trichophyton rubrum than the commercial cream. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.

/pdf/microemulsion-based-gel-of-terbinafine-for-the-treatment-of-2sbxggtol5.pdf

Microemulsion-Based Gel of Terbinafine for the Treatment of Onychomycosis: Optimization of Formulation Using D-Optimal Design

Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: ex vivo permeation and skin irritation studies.

Metformin hydrochloride exhibits poor compressibility during compaction, often resulting in weak and unacceptable tablets with a high tendency to cap. The purpose of this study was to develop directly compressible metformin hydrochloride by the spray-drying technique in the presence of polymer. Metformin hydrochloride was dissolved in solutions containing a polymer, namely polyvinylpyrrolidone (PVP K30), in various concentrations ranging from 0-3% (m/V). These solutions were employed for spray-drying. Spray-dried drug was evaluated for yield, flow property and compressibility profile. Metformin hydrochloride spray-dried in the presence of 2% PVP K30 showed an excellent flow property and compressibility profile. From the calculated Heckel's parameter (Py = 2.086), it was demonstrated that the treated drug showed better particle arrangement in the initial compression stage. Kawakita analysis revealed better packability of the treated drug compared to the untreated drug. Differential scanning calorimetry and Fourier transform infrared spectroscopy experiments showed that the spray-dried drug did not undergo any chemical modifications. Tablets made from the spray-dried drug (90%, m/m) were evaluated for crushing strength, friability and disintegration time and the results were found satisfactory.

/pdf/development-of-directly-compressible-metformin-hydrochloride-2bo9eunmdw.pdf

Development of directly compressible metformin hydrochloride by the spray-drying technique.

Compactibility improvement of metformin hydrochloride by crystallization technique

Onychomycosis is the most common nail disease affecting nail plate and nail bed. Onychomycosis causes onycholysis which creates cavity between the nail plate and nail bed, where drug formulations could be applied, providing a direct contact of drug with the nail bed facilitating drug delivery on the infected area. The purpose of the present study was to design and evaluate the potential of microemulsion-based gel as colloidal carrier for itraconazole for delivery into onycholytic nails for effective treatment of onychomycosis. Itraconazole-loaded microemulsions were prepared and optimized using D-optimal design. The microemulsion containing 6.24 % oil, 36 % Smix, and 57.76 % water was selected as the optimized batch (MEI). The globule size and drug loading of the optimized batch were 48.2 nm and 12.13 mg/ml, respectively. Diffused reflectance FTIR studies were performed to study drug–excipient incompatibility. Ex vivo permeation studies were carried out using bovine hoof and human cadaver skin as models for nail plate and nail bed, respectively. Microemulsion-based itraconazole gel (MBGI) showed better penetration and retention in human skin as well as bovine hoof as compared to commercial preparation (market formulation, MFI). The cumulative amount of itraconazole permeated from the MBGI after 12 h was 73.39 ± 3.55 μg cm−2 which was 1.8 times more than MF. MBGI showed significantly higher ex vivo antifungal activity (P < 0.05) against Candida albicans and Trichophyton rubrum when compared to MFI. Stability studies showed that MBGI was stable at refrigeration and room temperature for 3 months. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.

Punit B. Parejiya

Papers

Microemulsion-Based Gel of Terbinafine for the Treatment of Onychomycosis: Optimization of Formulation Using D-Optimal Design

Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: ex vivo permeation and skin irritation studies.

Development of directly compressible metformin hydrochloride by the spray-drying technique.

Compactibility improvement of metformin hydrochloride by crystallization technique

Microemulsion-based antifungal gel delivery to nail for the treatment of onychomycosis: formulation, optimization, and efficacy studies