Numerous methods have been developed to enhance transdermal drug permeation, e.g., iontophoresis, electroporation, ultrasound, ablation, along with chemical enhancers like, alcohols, terpenes, azones and, more recently, solvents such as dimethylsulfoxide (DMSO). Traditional delivery methods based on passive diffusion of drug molecules into the skin are unable to deliver macromolecules, such as peptides, vitamins, proteins, DNA and vaccines, due to the barrier properties of stratum corneum (SC). For this study we prepared a solidified reverse micellar carbopol gel formulation containing lipid-based microspheres loaded with sodium bicarbonate solution having a shell wall matrix of .03% CBD (cannabidiol 99.9%) as the deliverable. Since the selective permeability of skin presents the major hindrance to delivery of drugs, a solvent, DMSO, was added to the carbopol gel in order to eliminate epidermal barriers at the stratum corneum (SC). In SC, corneocytes are surrounded by a cell envelope composed of cross-linked proteins and a covalently bound lipid envelope/shell wall matrix and are embedded in lipid lamellar regions, which are oriented parallel to the corneocytes surface. The SC lipids play an essential role in maintaining and structuring the lipid barrier which affords protection against external insults and water loss through the skin and is the reason of skin's selective permeability. SC is also the chief barrier to passive diffusion of drug molecules.

In the present study, we developed an SLN formulation using Guggul lipid as main lipid component and diclofenac as a model drug and evaluated for physical parameters, transdermal drug permeation, stability, and pH to control anti-inflammatory activity with unique vitamin formulations. The developed formulations were compared with an established, commercial transdermal emulgel (CEG) containing diclofenac diethylammonium (Voltaren Emulgel). A carbopol gel formulation containing free diclofenac sodium (CG) was also prepared and evaluated for release. These results can prove to be useful in designing specific formulations for transdermal drug absorption of CBD compounds.

The epidermis, or the outermost, nonvascular layer of the skin, is derived from the embryonic ectoderm which varies in thickness from 0.07 to 1.4 mm and is not smooth. This is the 5th, or outmost layer of the skin, called, stratum corneum, which is composed of flattened, cornified, non-nucleated cells. Please note apparent presence of 'corneocytes' surrounding the hair shafts: These occur at different heights depending upon the evolution toward EOL (end-of-life) cycle. Corneocytes are constantly produced by the human body. Thus, this process, Cornification (which allows dead skin cells, or keratinocytes, to form a protective layer on the outermost dermis), is never-ending. Because corneocytes are evulsive and eruptive, these occur in different shapes, heights <in nm to mm> and sizes, over time, as live cells reach EOL and transform into keratinocytes. Each of these cells can, and do, have different shapes, thicknesses and sizes. The 120um microspheres with 3% shell wall matrix composition of CBD fixed in the shell wall matrix, once liberated from the wall matrix, are deposited into the cavernosa of the corneocytes/ keratinocytes leading to more effective delivery of the actives.