Preparation, In Vitro and In Vivo Studies of Vitamin B12 Loaded Implants

Abstract

Vitamin B12 (cyanocobalamin) is essential for normal RBC formulation, nerve, proteins in the body, certain enzyme reactions, and neurologic function. Vitamin B12 is given both as an oral supplement and intramuscular single dose with multiple and consecutive treatment in an injection. Long-acting formulations are required with the use of polymeric biodegradable implants. This study focuses specifically on the formulation of sterilized vitamin B12 loaded implants by using a biodegradable polymeric implant, poly-lactic glycolic acid (PLGA). In addition to the establishment of in vitro release of vitamin B12 as a function of time. One set of in vitro parameters to demonstrate in vivo serum concentration and release for implants using a single PLGA polymer in rats. Six sterilized different batches of vitamin B12 loaded implants were produced and only four of them were tested in vivo using rats’ models. It was found that B12 would not be adversely affected by potentially low pH environments. An in vitro release study of vitamin B12 from biodegradable polymeric implants was studied and followed over 50 days. Pharmacokinetic profile from PLGA implants were tested in rats for the four selected batches over 30 days to assess the prospect of creating a long term, sterile, drug delivery system for B12 supplementation. The onset was rapid and serum concentration was approximately 6-12 ng/ml at 10 days and decreased to about 2-4 ng/ml at 15 day and followed by increasing to ~28 ng/ml 30 days. Although implants were removed at 45 days, there was no detectable B12 in serum and this was consistent with residual B12 content in the extracted implants. This study demonstrates the stability of vitamin B12 against pH environment of the polymer degradation during the release study. Current results suggest that implants containing B12 could achieve appropriate release of medication within approximately one week and last for at least 45 days. This study is fundamentally representing a feasible and acceptable drug delivery system.