Author: Harneet Marwah ,Tarun Garg, Amit K. Goyal &Goutam Rath
74% of drugs are taken orally and are not found to be as effective as desired, to improve such characteristics, transdermal drug delivery was brought to existence, this delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery, several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system, Transdermal delivery system can transport the drug through skin into the blood circulation at fixed rate. Transdermal route gives an alternative to oral and i.v. delivery, local delivery is properly documented which includes targeted delivery, lower systemic exposure, and lower toxicity than oral medications. This system is also helpfull in the treatment of hair loss, neuropathic pain, acne, genital herpes, migraine, headaches, and sexual dysfunction, Transdermal delivery avoids the stomach environment where the drug can be degraded , Transdermal delivery avoids the first pass effect where active drug molecules can be converted to inactive molecules or even to molecules responsible for side effects, Provides steady plasma levels, easy to use and non-invasive, drug input can be stopped at any point after removal of the patch from the site , Increases compliance and reduces medical costs, Improves bioavailability, Best route for pediatrics patients, Suitable route for unconsious or vomiting patient, Lesser chances of overdose and easy detection of drug, Human skin: penetration barrier, Stratum corneum, Dermis, Hypodermis, Drug can be penetrated by three pathways such as transcellular route, paracellular lipid route and transappendgeal- route ,Transcellular Route: Moeity passes through both keratinocytes and lipids (straight path to the dermis), Paracellular Route: The most common penetration pathway of drug molecules. In this pathway, drug remains in lipid moeity and stay around keratin (easy for lipid soluble drug rather than proteins) , Transappendgeal Route: It makes continues channel for drug permeation but it hindered easily due to presence of hair follicles and sweat ducts, Physiochemical properties of the drug delivery system, release characteristics, drug release mechanism mainly depends on drug molecules which are dissolved or suspended in the delivery system and on interfacial partition coefficient or pH of the drug from delivery system to the skin tissue. If the drug is easily released from the delivery system, the rate of transdermal permeation will be higher, composition of drug delivery system, Composition may not affect release properties but may affect its permeability functionality. For example, methyl salicylate is more lipophilic than parent acid, and its percutaneous absorption is high when applied to skin in a lipoidal vehicle, Enhancement of transdermal permeation, majority of drugs will not permeate into skin for therapeutic use. Some enhancers are used for synergistic action without showings its properties), Strategies applied for permeation enhancement, drawback of transdermal delivery is permeation of active moeity through skin. So, various studies are done for enhancing its permeability percutaneously. Figure 3 depicts various strategies for increment of penetration. They act by three mechanisms: (1) By altering physicochemical properties of stratum corneum, (2) By changing hydrating property of stratum corneum, (3) By altering structure of lipids and protein in intercellular channel via carrier mechanism, Drug/vehicle interaction, Drug and prodrug selection, Active ingredient to be used should be judiciously chosen on the bases of pharmacological or physiochemical properties, Ideal properties for drug selection are: Less than 600 Da is preferred when diffusion coefficient is high, Good solubility in oil and water, High and adequate partition coefficient (13), Should carry melting point minor than 200?F, It should not metabolize in skin, Chemical enhancers help in permeation across the skin by disruption of the highly ordered structure of stratum corenum lipid, interaction with intercellular protein or improve partition of the drug into stratum corneum
