Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches.

The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin's stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach. Surmounting the significant barrier properties of the skin in a well-organised, momentary, and harmless approach is still challenging. Chemical permeation enhancers (CPEs) with higher activity are associated with certain side effects restricting their advancement in transdermal drug delivery. Furthermore, complexity in the interaction of CPEs with the skin has led to difficulty in elucidating the mechanism of action. Nevertheless, CPEs-aided transdermal drug delivery will accomplish its full potential due to advancements in analytical techniques, synthetic chemistry, and combinatorial studies. This review focused on techniques such as drug-vehicle interaction, vesicles and their analogues, and novel CPEs such as lipid synthesis inhibitors (LSIs), cell-penetrating peptides (CPPs), and ionic liquids (ILs). In addition, different types of microneedles, including 3D-printed microneedles, have been focused on in this review.

Systematic Optimization, In Vitro Drug Release, and Preliminary Nonclinical Toxicity Assessment of Nonphospholipid-Based Topical Ophthalmic Emulsions Containing 0.05 or 0.1% w/w Cyclosporin A for Dry-Eye Syndrome Management.

The objectives of the present investigations are (1) to envisage a risk assessment plan for nonphospholipid-based topical ophthalmic emulsions with the help of failure mode and effect analysis (FMEA), (2) to screen the risky formulation and process variables by the Taguchi design, (3) to optimize systematically an emulsion formula by face-centered central composite design (CCD), (4) to incorporate cyclosporin A (0.05 or 0.1% w/w) into the optimized emulsions and predict the in vitro drug release kinetic via a particle diffusion-controlled mathematical model equation, and (5) to assess the emulsion's toxicity using in vitro hemolysis study. Through the risk priority number (RPN) scores of FMEA, half-normal and Pareto charts of the Taguchi design, 3D-response surface graphs, and overlay plots of CCD, the emulsion formula was systematically optimized. Irrespective of the two different drug loadings into optimized emulsions, the drug entrapment efficiency values ranged from 73.20 ± 0.13 to 74.42 ± 0.15%. The film diffusion or ion-exchange process fails to interpret the in vitro drug release kinetic profile. A permissible percentage hemolysis value of above 10% but below 25% guidance was observed for emulsions with or without cyclosporin A. The systematically optimized phospholipidless ophthalmic emulsions could further be exploited commercially for managing dry-eye syndrome.