Author K Sharma
hypertension is a chronic disease, which requires long-term treatment with drug therapy at steady state drug blood concentration. Candesartan cilexetil (CC) is a prodrug that is rapidly converted to candesartan (its active metabolite) during absorption from the gastrointestinal tract and confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II. It has a molecular weight of 610.66 with poor oral bioavailability, the patients requiring further reduction in blood pressure should be titrated to 32 mg, the major disadvantages of such a drug therapy are more frequency of administration, extensive first pass metabolism and variable bioavailability which make it an ideal candidate for transdermal drug delivery systems. This explains the need of anti-hypertensive transdermal patches in the perspective of enhancing the bioavailability as well as in improving patient compliance Transdermal drug delivery system allows delivery of contained drug into the systemic circulation via permeation through skin layers at a controlled rate. These systems are easy to apply and remove as and when desired. However, the protective upper layer of the skin, stratum corneum (SC) behaves like a challenging barrier for the penetration of majority of drugs, It offers a formidable physical barrier to molecular transport, This layer is very specific with regards to the type of molecule that can be transported across the skin, and therefore, only molecules with certain physicochemical properties can readily cross the skin, this limits the range of potential drugs that can be administered transdermal, which emphasizes the need for formulations to incorporate penetration enhancers to assist in the effective delivery of a larger variety of drugs across the skin, the use of herbal penetration enhancers which penetrate into human skin and shows reduction in the barrier resistance is widely accepted in transdermal drug delivery. The mechanism behind enhanced penetration rate of drugs across the skin is through two possible mechanisms of action. First, the penetration enhancer can work by altering the solubility properties of the skin, thereby increasing the solubility of the drug within the SC; second, the enhancer disrupts the ordered nature of the skin lipids, which consequently influences diffusion across the SC, Nowadays, many herbal penetration enhancers are included in generally recognized as safe substances list, and they possess low side effects and irritancy in comparison with synthetic chemicals such as solvents and azones or surfactants, One such a natural product, Aloe vera (Aloe barbadensis Miller) gel, has shown potential to enhance the permeation of certain drug molecules through skin membranes. Aloe Vera Gel gel is the viscous, transparent, and colorless mucilaginous gel obtained from the parenchymatous cells in the fresh leaves. It was suggested that the mucilaginous gel of the aloe, consisting mainly of polysaccharides, holds the secret to some of the medicinal properties and biological effects of this family of plants, which was confirmed for drug absorption enhancement across intestinal epithelial cells. Aloe Vera Gel has an element called Lignin which helps it to penetrate right down to the cellular level. It also has another element called Saponin which works as a natural cleansing agent. Both these elements working in conjunction reach the cellular level of the skin. In addition to this, it also nourishes the skin and replenishes it with the much-needed nutrition that it requires, s, it increases the in vitro skin penetration of some compounds depending on their molecular weights with an apparent inverse correlation between enhancement ratio and molecular weight of the compound. This penetration enhancement effect of the aloe gel was explained by a probable pull effect of complexes formed between the compound and the enhancing agent within the aloe gel but it was stated that the proposed mechanism of action
