The current study involves development of oral bioadhesive hydrophilic matrices of hydralazine hydrochloride, and optimization of their in vitro drug release profile and ex vivo bioadhesion against porcine gastric mucosa. A 32 central composite design was employed to systematically optimize the drug delivery formulations containing two polymers, viz., carbomer and hydroxypropyl methyl cellulose. Response surface plots were drawn and optimum formulations were selected by brute force searches. Validation of the formulation optimization study indicated a very high degree of prognostic ability. The study successfully undertook the development of an optimized once-a-day formulation of hydralazine with excellent bioadhesive and controlled release characteristics.