Release and absorption rates of intramuscularly and subcutaneously injected pharmaceuticals (II)

Abstract

The rate and extent of intramuscular (i.m.) and subcutaneous (s.c.) drug absorption are very erratic and variable. The lipophilicity of the compound plays an important role. Aqueous drug solutions and suspensions of the more lipophilic compounds are often absorbed incompletely within the therapeutically relevant time. More hydrophilic compounds are absorbed completely. Injection depth, drug concentration and vehicle volume, pH-p K a relation, vehicle, cosolvents and surfactants have strong influences on the absorption profile of lipophilic drugs. Aqueous solutions of hydrophilic drugs are less sensitive to these factors. Drug solutions in oil and even suspensions in oil are often thought to be sustained release preparations. In fact, rapid absorption has often been observed. Slow release is not a property of the oily vehicle but is achieved by a high lipophilicity of the dissolved or suspended compound. Liposomal preparations are currently under investigation as i.m. and s.c. injectable sustained release preparations. Factors that induce drug release at the injection sites are the proteins and especially lipoproteins in the interstitial fluids, originating from serum filtrate and from turnover of inflammatory cells. Phagocytosis by macrophages and fat cells may play an important role in the local clearance of liposomal material from the injection site. Sustained release of some pharmaceuticals with normal or long half-lives appeared in specific cases preferable to rapid release. In addition, high arterial drug concentrations during the absorption phase may result in undesired effects even when venous drug concentrations are within the safe range.