Insulin remains indispensable in the management of diabetes mellitus since its discovery in 1921. The foreignness of early available porcine and bovine insulin led to the development of human insulin by transpeptidation and biosynthesis in microorganisms. Needle phobia and stress of multiple daily injections led to the investigation and exploitation of all promising routes, ranging from nasal to rectal, by a wide variety of devices and delivery systems. This article describes the development of human insulin, various routes for delivery of insulin (including oral, nasal, buccal, rectal, and pulmonary), and various devices for regulated, safe, and convenient insulin delivery. The article reviews some recent advances in insulin delivery such as the bioresponsive and self-regulated insulin delivery system.
Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers Eudragit RL 100, ethyl cellulose, PVP K-30, and polyvinyl acetate, and citral was used as the penetration enhancer. The polymer fi lms were formulated with Eudragit RL 100 and PVP K-30 in different ratios and subsequently subjected to ex vivo studies (drug permeation through rat skin) followed by interaction studies, skin irritation studies, accelerated stability analysis, and in vivo studies (determination of blood glucose level in rabbits). The drug content of the formulations was found to be 99.1-99.2%. The cumulative percentages of drug permeated through rat skin from the three selected formulations in 48 h were 95.3%, 98.8%, and 99%, respectively. A plot between cumulative percent of drug permeated and square root of time exhibited linear curves, which suggests the Higuchian matrix mechanism of drug release. The formulation containing Eudragit RL 100 and PVP K-30 showed better improvement in hypoglycemic activity in rabbits (56.2-60.8% reduction in blood glucose level, p < 0.05). There were fewer fluctuations in blood glucose level as compared to oral therapy due to controlled release of the active pharmaceutical ingredient, and no interaction was found between the drug and excipients of the formulation. Accelerated stability analysis showed that the formulation was stable up to 5.5 years, with negligible skin irritation. The formulation precluded severe hypoglycemic reactions (side effect of sulfonylureas) and was effective for management of diabetes mellitus up to 48 h, with a single TTS.
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