Browsing Research, Student by Author "Bakshi, Pooja"
Facilitated Delivery of Pharma- and Cosmeceuticals into Skin and Drug DisposalBakshi, PoojaTransdermal drug delivery (TDD) has several advantages over other delivery approaches, offering a non-invasive route that bypasses first pass metabolism and provides sustained plasma drug levels. The global impact of the TDD industry has increased tremendously in the last few years. For effective TDD delivery, or for a drug to exert its activity, it needs to be delivered across the stratum corneum (SC). However, SC, the outermost layer of the skin, forms a formidable barrier that limits the delivery of drugs through skin, especially large and hydrophilic molecules such as peptides and polysaccharides. For a drug to be delivered passively via the transdermal route it should, ideally, be moderately lipophilic and have a molecular weight of <500 Daltons. The type of vehicle and formulation characteristics play a key role in delivering the required concentrations of various drugs across this barrier. As a result, different strategies have been developed and explored to enhance drug delivery, into and through skin. In our studies, we investigated the delivery of different pharma- and cosmeceuticals into the skin by screening various excipients to formulate effective delivery systems for their enhanced delivery. The first aim included performance of mechanistic studies using chemical penetration enhancers (CPE), commonly used for topical and transdermal drug delivery. Studies such as histology, Fourier-transform infrared spectroscopy (FTIR), and microscopic evaluation provided a better insight about the mechanism and efficiency of CPEs. These studies are important tools to evaluate interactions between the drug, enhancer, and skin and are useful to determine if a specific CPE can be used for targeted drug delivery. Thus, understanding the mechanism of CPEs, can enable the selection of a suitable vehicle in order to achieve targeted delivery for topical and transdermal formulations. The second aim included development of a topical formulation for the passive delivery of a large hydrophilic molecule, heparinoid, across human skin. Various topical formulations, incorporating both hydrophilic and lipophilic penetration enhancers were formulated and screened for enhanced delivery of heparinoid in the skin. In vitro permeation of the formulation (s) was/were performed and a cell culture model was used to evaluate its irritation potential. The optimized formulation was then compared to the commercially available marketed formulations (cream, gel, ointment) in terms of skin permeation. Delivery of topicals can be enhanced further with the aid of delivery techniques, such as iontophoresis, ablative laser, and microdermabrasion. In our third aim, different enhancement strategies commonly used in the cosmetic or dermatological clinics, such as microdermabrasion, ablative laser, iontophoresis, and combination of laser and microdermabrasion, and laser and iontophoresis, were employed for improving the topical delivery of a cosmeceutical agent. Argireline, an anti-aging peptide, used as a Botox substitute was the molecule investigated in this study. Lastly, a novel drug disposal system consisting of a pouch containing granular activated carbon packaged within a water-soluble film reservoir was evaluated for its efficiency to deactivate unused medications. This system is designed to be used for disposal of unwanted medications, which is a major problem leading to unintentional risks of exposure and added environmental waste. In our fourth and fifth aim, we investigated the deactivation efficiency of the system for the disposal of various psychoactive model drugs. We also tested the deactivation profile of drugs (ranging from Schedule II to Schedule IV category) from different dosage forms such as tablets and capsules. Prior to analyzing the amount of the drug deactivated, stable and sensitive high performance liquid chromatography (HPLC-UV) analytical methods for methylphenidate hydrochloride and loxapine succinate, two model psychoactive prescription medications, having a high abuse potential, were developed and validated. In addition to psychoactive drugs, deactivation efficacy for fentanyl transdermal patches was evaluated as part of the fifth aim of our study. Our results demonstrated that the type of excipients (permeation enhancers or vehicle) incorporated in the formulation as well as the type of delivery strategy employed, can markedly affect the permeation of the actives into the skin. In addition, our data established the efficacy of the unique drug disposal system by demonstrating the deactivation profile of some highly-abused drugs.