Enhanced Skin Deposition of Betamethasone Dipropionate from a Novel Formulation and Drug Delivery Technology.

INTRODUCTION: Effective topical drug delivery is the essence of dermatologic treatment. The drug must be applied to the skin surface, be released from the vehicle, enter the stratum corneum, traverse the epidermis, and enter the dermis pharmacologically intact. New advances have improved emulsion-type formulation and drug delivery technology by encapsulating dispersed oil droplets in a robust multimolecular aqueous film of surfactants, oil, and water, enabling a multifold decrease in surfactant concentration compared to conventional creams. In the research reported here, we studied this new concept, termed polyaphron dispersion (PAD) technology, by comparing skin delivery of betamethasone dipropionate from a novel oil-in-water emulsion system of calcipotriene and betamethasone dipropionate (CAL/BDP) cream to that from a traditional topical suspension (CAL/BDP TS) utilizing in vitro and in vivo detection methods. METHODS: The amount of BDP released from the CAL/BDP cream and CAL/BDP TS was evaluated using both in vitro Franz cell analysis and in vivo human tape stripping from ten female human volunteers after a single application of CAL/BDP cream or CAL/BDP TS. For the tape stripping analysis, 20 circular tape strips were taken from forearm application sites at 1, 2, 4, and 8 h after application and analyzed for the amount of BDP in the tape strip using liquid chromatography-mass spectrometry (LC-MS). RESULTS: The in vitro Franz cell analysis demonstrated that the cumulative amount of BDP that diffused through the epidermis was statistically significantly greater for the CAL/BDP cream compared to the CAL/BDP TS at all time points. In addition, consistently higher amounts of BDP were recovered following CAL/BDP cream application than following CAL/BDP TS application at 1, 2, 4, and 8 h following application utilizing the in vivo tape stripping technique. CONCLUSION: The novel PAD technology-based cream formulation delivered more BDP into the upper stratum corneum and lower epidermis than a traditional topical suspension.

Polyaphron Dispersion Technology, A Novel Topical Formulation and Delivery System Combining Drug Penetration, Local Tolerability and Convenience of Application.

Topical formulation and delivery technologies for pharmaceutical application should simultaneously address efficacy, safety and convenience of therapy. This has historically proven to be challenging, since formulation features that drive efficacy often have undesirable consequences for safety and convenience and vice versa. Polyaphron dispersion (PAD) technology is a novel topical formulation and drug delivery system developed with the purpose of preserving these key attributes. PAD formulations are typically oil-in-water dispersions consisting of oil droplets encapsulated in a multi-molecular shell structure. This shell structure protects potentially unstable active molecules solubilized in the oil from hydrolytic degradation. Example data are presented of enhanced drug penetration from PAD formulations, including dermal delivery of calcipotriene, betamethasone dipropionate and tacrolimus as well as ocular delivery of ciclosporin A. Local tolerability is an important safety parameter for topical formulations, where high levels of surfactants can cause skin irritation. In this regard, a key benefit of PAD formulations is the inherent reduced requirement for surfactants to generate stable formulations compared to conventional emulsion systems. Patients with chronic diseases with topical manifestations such as psoriasis or atopic dermatitis have been reported to miss up to 70% of planned topical applications, mainly due to a lack of satisfaction with their therapy. Patients generally prefer light, moisturizing, non-greasy and quickly absorbed vehicles that are simple to use on all body parts. PAD formulations can generally be designed to meet these criteria. In conclusion, PAD technology provides high flexibility in topical drug design and can be applied to several body locations without compromising efficacy, safety or convenience of therapy.Clinical Trial Register: Clinicaltrials.gov: NCT03802344.

Polyaphron Formulations Stabilised with Different Water-Soluble Polymers for Ocular Drug Delivery.

As drug delivery to the eye has evolved over the last decades, researchers have explored more effective treatments for ocular diseases. Despite this, delivering drugs to the cornea remains one of the most problematic issues in ophthalmology due to the poor permeability of the cornea and tear clearance mechanisms. In this study, four different types of polyaphron formulations are prepared with 10% poloxamer 188 (P188), 10% poly(2-ethyl-2-oxazoline), 1% polyquaternium 10, and 3% sodium carboxymethylcellulose solutions mixed with 1% Brij® L4 in a caprylic/capric triglycerides solution. Their physicochemical characteristics, rheological properties, and stability are assessed. Additionally, a polyaphron with 3% polyquaternium 10 was prepared for the assessment of ex vivo corneal retention along with four other polyaphrons. The best retention on the ex vivo cornea was displayed by the 3% polyquaternium 10-based formulation. The 10% poloxamer 188 along with 1% polyquaternium 10-based polyaphrons appeared to be the most stable among the four prepared formulations. A toxicological evaluation of these formulations was performed using a slug mucosal irritation test and bovine corneal opacity and permeability assay, with all four polyaphrons proving good biocompatibility with ocular tissues. The developed drug delivery systems demonstrated an excellent potential for ocular drug delivery.

Penetration Enhancers in Ocular Drug Delivery.

There are more than 100 recognized disorders of the eye. This makes the development of advanced ocular formulations an important topic in pharmaceutical science. One of the ways to improve drug delivery to the eye is the use of penetration enhancers. These are defined as compounds capable of enhancing drug permeability across ocular membranes. This review paper provides an overview of anatomical and physiological features of the eye and discusses some common ophthalmological conditions and permeability of ocular membranes. The review also presents the analysis of literature on the use of penetration-enhancing compounds (cyclodextrins, chelating agents, crown ethers, bile acids and bile salts, cell-penetrating peptides, and other amphiphilic compounds) in ocular drug delivery, describing their properties and modes of action.