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Purpose: To study the release behaviour of ciprofloxacin hydrochloride tablet matrices prepared with different polymers in dissolution media of different pH. Methods: Different formulations of slow-release matrix tablets of ciprofloxacin hydrochloride were prepared with polymers, namely, ethyl cellulose (Etc), hydroxyethyl cellulose (Hec), hydroxypropyl methylcellulose (Hpc), and Eudragit® L-100 (Eud) using matrix embedding technique. The matrix tablets were characterized and studies of their dissolution profiles were studied in 0.1 N HCl (pH 1.2) and in simulated intestinal fluid (excluding enzymes) of pH 4.0, 6.0, and 7.4. Results: The tablets had the following characteristics: weight, 659.25 ± 7.96 to 661.65 ± 6.53 mg; hardness, 7.05 ± 0.21 to 9.60 ± 0.40 kgf; friability, 0.212 to 0.292 %; and drug content, 91.47 ± 0.53 to 112.50 ± 4.14 %. In batches prepared with ethyl cellulose, Eudragit L-100, and hydroxypropyl methylcellulose, drug release increased with a decrease in pH. However, matrix tablets prepared with hydroxyethyl cellulose displayed the highest drug release at pH 4.0 with Cmax of 108.75 % and T50% of 30.86 min; thereafter, drug release decreased with increase in pH. The pattern of drug release was Hec > Hpc > Eud > Etc in most media with more drug release in acidic than at alkaline pH. Conclusion: Release of ciprofloxacin from the formulated matrix tablets was pH-sensitive in vitro. This should be taken into consideration in designing sustained release oral form of ciprofloxacin.