The overall objective of the program is to develop a new more economical sustained action injectable formulation of -buprenorphine, based on microcapsules prepared by BIOTEK's air suspension process. The microcapsules will be used in a large placebo controlled study in Phase II of the SBIR program. Recently we tested 30-day buprenorphine microcapsules in five (5) heroin addicts at the Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit. For all five subjects the depot buprenorphine medication appeared to provide remarkable relief from opioid withdrawal without evidence of intoxication or respiratory depression over the six weeks of post-depot observation and assessment. Furthermore, the formulation was very effective in dramatically reducing responsiveness to exogenous opioid challenge for a duration of at least several weeks. Clinically, all five participants successfully achieved opioid detoxification, without other medications for withdrawal relief, and without clinically significant withdrawal signs or symptoms. During the subsequent 2-week outpatient phase all patients reported abstinence from opioids and urine toxicology samples were negative for opioids. These remarkable and very exciting findings compel us to drive forward and expand and accelerate the testing of depot buprenorphine in a large population of heroin addicts with appropriate placebo controls. Support is sought under the SBIR program to develop and optimize a more economic formulation of depot buprenorphine microcapsules, by using a new process which produces a much higher yield (5-6 fold increase) of microcapsules in the injectable size range. In preliminary studies detailed in this application, we have demonstrated significant reduction in manufacturing costs and the equivalency of the buprenorphine release profile from the old and new formulation. During Phase II of the SBIR program, microcapsule development will be completed, a large number of vials will be prepared under cGMP. The current IND will be updated and submitted to the FDA with a clinical protocol to test the formulation in a larger population of heroin addicts with appropriate placebo controls.
A sustained action opioid agonist/antagonist formulation, such as microencapsulated buprenorphine would be a significant advance. Once a month treatment is an economic advantage and allows staff members to devote more time to patients and less to dose administration. This formulation will provide opioid antagonism like that of naltrexone, but there would be less motivation for the post addict to drop out of therapy due to the agonistic action similar to that of methadone or LAAM. The overall treatment plan would not need to revolve about a rigid dosing schedule. Rather treatment could be designed to best benefit the patient, and an example of habitual drug taking behavior is eliminated. The drug thus becomes an adjunct not the major aspect of therapy.
