Drug Delivery via the Mucous Membranes of the Oral Cavity

Absorption of Some Organic Compounds Through the Skin in Man

The purpose of this review is to give an insight into the considerable potential of lecithin organogels (LOs) in the applications meant for topical drug delivery. LOs are clear, thermodynamically stable, viscoelastic, and biocompatible jelly-like phases, chiefly composed of hydrated phospholipids and appropriate organic liquid. These systems are currently of interest to the pharmaceutical scientist because of their structural and functional benefits. Several therapeutic agents have been formulated as LOs for their facilitated transport through topical route (for dermal or transdermal effect), with some very encouraging results. The improved topical drug delivery has mainly been attributed to the biphasic drug solubility, the desired drug partitioning, and the modification of skin barrier function by the organogel components. Being thermodynamically stable, LOs are prepared by spontaneous emulsification and therefore posses prolonged shelf life. The utility of this novel matrix as a topical vehicle has further increased owing to its very low skin irritancy potential. Varied aspects of LOs viz formation, composition, phase behavior, and characterization have been elaborated, including a general discussion on the developmental background. Besides a comprehensive update on the topical applications of lecithin organogels, the review also includes a detailed account on the mechanistics of organogelling.

Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: A review

Transdermal drug delivery system has been in existence for a long time. In the past, the most commonly applied systems were topically applied creams and ointments for dermatological disorders. The occurrence of systemic side-effects with some of these formulations is indicative of absorption through the skin. A number of drugs have been applied to the skin for systemic treatment. In a broad sense, the term transdermal delivery system includes all topically administered drug formulations intended to deliver the active ingredient into the general circulation. Transdermal therapeutic systems have been designed to provide controlled continuous delivery of drugs via the skin to the systemic circulation. The relative impermeability of skin is well known, and this is associated with its functions as a dual protective barrier against invasion by micro-organisms and the prevention of the loss of physiologically essential substances such as water. Elucidation of factors that contribute to this impermeability has made the use of skin as a route for controlled systemic drug delivery possible. Basically, four systems are available that allow for effective absorption of drugs across the skin. The microsealed system is a partition-controlled delivery system that contains a drug reservoir with a saturated suspension of drug in a water-miscible solvent homogeneously dispersed in a silicone elastomer matrix. A second system is the matrix-diffusion controlled system. The third and most widely used system for transdermal drug delivery is the membrane-permeation controlled system. A fourth system, recently made available, is the gradient-charged system. Additionally, advanced transdermal carriers include systems such as iontophoretic and sonophoretic systems, thermosetting gels, prodrugs, and liposomes. Many drugs have been formulated in transdermal systems, and others are being examined for the feasibility of their delivery in this manner (e.g., nicotine antihistamines, beta-blockers, calcium channel blockers, non-steroidal anti-inflammatory drugs, contraceptives, anti-arrhythmic drugs, insulin, antivirals, hormones, alpha-interferon, and cancer chemotherapeutic agents). Research also continues on various chemical penetration enhancers that may allow delivery of therapeutic substances. For example, penetration enhancers such as Azone may allow delivery of larger-sized molecules such as proteins and polypeptides.

Drug delivery systems. 6. Transdermal drug delivery.

Cytotoxicity of Ophthalmic Preservatives

Review ArticlePercutaneous absorption

Effectiveness of antibacterial agents presently employed in ophthalmic preparations as preservatives against pseudomonas aeruginosa.

Glycerin and sorbitol were found to supplement each other in their inhibition of both molds and bacteria. It is believed that this inhibitory action is purely one of osmotic effect. Propylene glycol appears to have a specific inhibitory effect against bacteria and most molds; the addition of 10% w/v propylene glycol was found to inhibit the growth of these organisms. Thirty per cent w/v propylene glycol is required to inhibit Monilia albicans. Studies have indicated that the inhibition produced by the addition of propylene glycol to sorbitol solutions is not purely the result of osmotic effect, as is the case with glycerin, but probably one related to its chemical structure. It may, therefore, be concluded that propylene glycol has a significant and useful preservative activity in many preparations including those made with sorbitol.

A study of the inhibitory concentrations of glycerin‐sorbitol and propylene glycol‐sorbitol combinations on the growth of microorganisms

An approach to the evaluation of the percutaneous absorption of drugs from ointment bases is described. Salicylic acid and sodium salicylate were selected as test drugs for incorporation into ointment bases representing each of four physical types of ointment vehicles. These ointments were applied to the intact shaved skin of the rabbit and confined by a specially designed bandage. Concentration of salicylate in the blood was determined at hourly intervals following application of the ointment. Salicylic acid was most effectively absorbed from hydrophilic ointment. The extent of absorption from the other ointments studied, in decreasing order, was: hydrophilic petrolatum containing water, petrolatum, and polyethylene glycol ointment. Sodium salicylate was also absorbed to the greatest extent from hydrophilic ointment, although the degree of absorption was considerably less than that observed with salicylic acid. On the basis of salicylate blood levels, no significant absorption of sodium salicylate occurred from ointments prepared with petrolatum, hydrophilic petrolatum containing water, or polyethylene glycol ointment.

The effect of various ointment bases on the percutaneous absorption of salicylates. I. Effect of type of ointment base.

Forty-eight substances and combinations were studied for their possible effectiveness as preservatives for solutions of nonionic surfactants of the sorbitan partial fatty acid ester and polyoxyethylene ester types. Results indicated that sorbic acid (0.2 per cent w/v); phenylmercuric borate (0.007 per cent w/v); phenylmercuric nitrate (0.01 per cent w/v); phenylmercuric acetate (0.007 per cent w/v); n -trichloromethylmercapto-4-cyclohexene-1,2-dicarboximide (Vancide® 89 RE, 0.04 per cent w/v); diethylene glycol monomethyl ether (methyl Carbitol, 3 per cent w/v); hexylene glycol (3 per cent w/v); and benzalkonium chloride (0.1 per cent w/v) are effective in preserving these solutions. The failure of various phenolic preservatives to preserve these surfactant solutions is attributed to complex formation between phenolic and polyether groups. Studies on various cosmetic formulations containing nonionic surfactants indicate that sorbic acid (0.2 per cent w/w) and combinations of sorbic acid and hexylene glycol are effective preservatives. These preservatives were also found effective in products containing sorbitol as well as nonionic surfactants.

The preservation of aqueous preparations containing nonionic surfactants II. Preservative studies in solutions and products containing nonionic surfactants

Martin Barr

Papers

Review ArticlePercutaneous absorption

Effectiveness of antibacterial agents presently employed in ophthalmic preparations as preservatives against pseudomonas aeruginosa.

A study of the inhibitory concentrations of glycerin‐sorbitol and propylene glycol‐sorbitol combinations on the growth of microorganisms

The effect of various ointment bases on the percutaneous absorption of salicylates. I. Effect of type of ointment base.

The preservation of aqueous preparations containing nonionic surfactants II. Preservative studies in solutions and products containing nonionic surfactants