Osmotic Implants

A dmg-dedicated osmotic implant for human and veterinary use has been developed to dehver hormones, peptides, and proteins that are digested or rendered inactive after oral adrninistration (106). 

Stevenson CL, Theeuwes F, and Wright JC. Osmotic implantable delivery systems. In Wise DL, ed. Handbook of Pharmaceutical Controlled Release Technology. New York, Basel Marcel Dekker, 2000, pp. 225-253. 

Osmotic implants—Controlled drug concentration release at physiological temperature for extended periods of time. 

Eckenhoff et al. (1990) prepared osmotic implant devices containing PST in a glycerol, gelatin, and L-histidine gel. The device had an exit passageway for the gel and separate compartments for the osmotic driving excipients and the PST gel. The in vitro dissolution studies demonstrated controlled release for a 2-month period. 

There have been recent studies on the importance of NO in modulating skin blood flow in both normal animals and in inflammatory models. Khan etiU. (1993), using laser-Doppler techniques, showed that the NOS inhibitor L-NAME inhibited rabbit ear blood flow. It was possible to do this chronically for up to 2 weeks using implanted osmotic pumps. Pons et id. (1993) also used laser Doppler to show that the vasodilator eflFect of LPS in rabbit skin, which mimics the efiect of Gram-negative bacteria, was likely to involve both i-NOS and IL-1. We have already discussed the damaging eflPects of neutrophils... 

Osmotic systems have application in pharmacological studies, implantation therapies, and oral drug delivery. 

Some implantation devices have extended well beyond the classic diffusional systems and have included not only bioerodible devices, but also implantable therapeutic systems that can be activated. There are devices activated by change in osmotic pressure to deliver insulin [225], morphine release trigger by vapor pressure [226], and pellets activated by magnetism... 

Drug solutions and implantation of osmotic mini-pumps Physostigmine hemisulphate and procyclidine hydrochlorid were obtained from Sigma (St.Louis, U.S.A.), scopolamine hydrobromid from Merck (Darmstadt, Germany), atropine sulphate was obtained from ACF (Amsterdam, The Netherlands), and diazepam from Roche (The Netherlands). HI-6 was made available by the Defence Research Establishment, Suffield, Canada. Soman (O-pinacolyl methylphosphonofluoridate) was synthesised at TNO. Alzet Osmotic Mini-pumps with a constant delivery rate of 0.55 pl/hr (Model 2002, Alza Corp., Palo Alto, USA) were used to deliver PYR, PHY and SCO. The vehicle consisted of 20% propylene glycol, 10% ethanol and 70% water. The pumps were implanted subcutaneously under isoflurane/02 inhalation anesthesia. 

Larson et al. (1996) investigated the ability of acute chloroform vapor exposure to produce toxicity and regenerative cell proliferation in the liver of female B6C3F, mice. Groups of 5 animals were exposed to 0, 0.3, 2, 10, 30, or 90 ppm chloroform via inhalation for 6 hours a day for 4 consecutive days. Animals were administered BrdU via an implanted osmotic pump, and cell proliferation was quantitated as the percentage of cells in S-phase (LI) measured by immunohistochemical detection of BrdU-labeled nuclei. 

---