eEvaluation of N- Hydroxymethyl Chlorphensin Carbamate and Ethionamide as Potential Prodrugs

Abstract

Chlorphensin carbamate is a centrally acting muscle relaxant, insoluble in water, readily absorbed from the gastro-intestinal tract , when administered orally and highly metabolized. The mechanism of action is by depressing spinal polysynaptic reflexes . Neuronal conduction, neuromuscular transmission and muscle excitability are not depressed except after nearly lethal l doses. This action led to its characterisation as inter-neuronal blocking agent and therefore used to relief symptomatic muscular spasm, treat osteoarithritis of hand or hip and trigeminal neuralgia. Ethionamide is a drug that is readily absorbed from the gastro-intestinal tract and i s extensively metabolized, so that less than one percent of it is excreted as active form in urine. The drug is anti-tubercular against mycobacterium balnei; and its action is bacteriostatic and in high concentration, it becomes bactericida and therefore used to tract pulmonary tuberculosis, peritonitis tuberculosis and leprosy. In the present study, N-hydroxymethyl chlorphensin carbamate and ethiomamide were synthesised and evaluated as potential prodrugs. This was done by studying their aqueous solubilities intrinsic dissolution rates, apparent partition co-efficients and their kinetics of decomposition in buffer systems. The results obtained showed the N-hydroxymethyl derivatives to possess higher water solubilities, higher intrinsic dissolution rates and lower lipophilicity than the parent compounds. The rate of decomposition to formaldehyde and the parent compound followed first-order kinetics and it is suggested that N-hydroxymethylation may be a potential useful means of obtaining prodrug forms of chlorphensin carbamate and ethionamide.