Palmitic acid as an excipient in implants for sustained release of insulin.

Abstract

Sustained-release implants for insulin can be made by compressing a powder admixture with palmitic acid as the excipient. At less than 20%, insulin does not disperse uniformly in the admixture. The size distribution of the excipient particles obtained after grinding for 15 min does not affect the sustained release action. When tested in a 33 d period, an 1/8-size piece (approximately 25 mg) implant cut from a pellet disc containing 20% insulin which is 13 mm in diameter and 1.5 mm thick released 0.12-0.17 mg insulin/d in diabetic Wistar rats. The 1/8-size piece containing 20% insulin or a rod of similar weight with a diameter of 3 mm, which can be inserted by a trocar, was optimal for the implant to provide a service-life of 49 +/- 7 d. The service-life decreased with progressive reduction in implant size. The implant functioned just as well subcutaneously or intraperitoneally and was eroded subcutaneously by 33.6-53.1% in 33 d. The glycosylated haemoglobin contents of diabetic animals on implant therapy which had a blood glucose level of 4.7 +/- 2.5 mmol/l were in a range of 6.2-8.9% compared to the control value of greater than 13% with chronic hyperglycemia. The overall results indicated that the implant was a promising alternative to daily insulin injections.