Formulations with HPMC K100LV and HPMC K15M grades show poor swelling and sustained action due to the low viscosity. These polymer grades are unable to withhold swelling produced by a swelling agent in the tablets due to the poor gelling/viscosity. The HPMC K100M showed good tablet integrity, swelling, and sustained release of ciprofloxacin HCl.
Swelling agents used in this study are super disintegrating agents. The immediate tablet disintegration is due to the swelling nature of these agents. This character is utilized in the preparation of floating, swellable, and extended release dosage form of ciprofloxacin HCl (24
Sodium bicarbonate in the acidic environment reacts with the acid and produces carbon dioxide. The evolved gas will get entrapped in the matrix leading to floating of the tablet. The floating lag time decreased as the concentration of the sodium bicarbonate increased. The formulations (F12, F13, and F14) containing different swelling agents with optimized concentration of polymer, swelling agent and sodium bicarbonate show different lag time. This may be due to variation in the mechanism of action of different swelling agents. CS and CCS produced its action by both swelling and wicking in the presence of water, whereas SSG shows only swelling. Wicking is caused due to the porosity and capillary action because of which the density of dosage form is reduced. The total duration of floating is also changed with change in swelling agent. Formulations F2, F10, and F13 show high lag time and fluctuations in floating.
The percentage swelling of the tablet is high, and it is obtained within 3-h interval in formulations F1, F5, F6, F7, F8, F9, and F12, which contain CP than the formulations with CCS, SSG, and STR. This is due to the swelling and wicking nature of CS. Swelling is low in case of formulations (F4, F11, and F14) containing CS as swelling agent which is due to highest swelling nature because of which tablet erodes. At the highest polymer concentration, the CCS shows good swelling than the tablet containing equal amounts of CCS and low concentrations of polymer F3 and F14 with polymer concentration as 25% and 15% w/w of that of drug, respectively. At a low concentration, the CCS (F11) shows good integrity, but the maximum swelling is less (15% swelling) which may not satisfy the conditions required for gastric retention.
The formulations containing SSG (F2 and F13) show the good swelling nature, but the maximum swelling will occur at later hours, i.e., in formulation F2, swelling 233.36% is obtained in 24 h interval, and for F13, the maximum swelling 178.73 is obtained in 5-h interval. The swelling at later hours may be due to gelling of SSG with water. STR (F4) shows poor swelling nature.
The formulations (F1 to F4) that contain polymer concentration 25% w
that of the drug show more retarded release, i.e., 69.19
2.9, and 60.01
3.2% release in 12 h of the formulations F1, F2, F3, and F4, respectively. The polymer HPMC K100M concentration is optimized to 15% w
that of drug. Further, the change in swelling agent concentration changes the drug release in formulation. The decrease in swelling agent concentration retards the drug release. The drug release is also dependent upon the type of swelling agent in the F12, F13, and F14, which releases 97.33
1.9, and 97.85
3.3%, respectively, in 8 h interval is shown in Fig. c. Increase in sodium bicarbonate concentration increases release rate.
The regression coefficient (R2
) values of release data of all formulations obtained by curve fitting method for zero-order, first-order, and Higuchi model are reported in Table . Most of the formulations follow the zero order and Higuchi model. For the optimized formulation F12, the R2
value of Higuchi 0.9806 (nearer to 1) is dominant than the other models which indicates that the drug release depended on the square root of the time (Eq. 4
The mechanism of drug release is predicted by using Eq. 5
according to Krosmeyer–Peppas. The n
value of optimized formulation F12 is 0.66 and that of all formulations is between “0.45 to 0.85”. This indicates that the drug release depends on swelling, erosion, and diffusion. All formulations follow the non-Fickian/anomalous type of diffusion.
The similarity factor f2
value of optimized formulation F12 is found to be 26.714, which indicates lack of similarity with marketed product (CIFRAN OD® 500 mg). The 92.8
11.5% drug release within 5 h interval is observed for marketed product.
The in vivo
nature of the tablet is observed in the radiographic pictures at different time intervals. Initially, the tablet appeared very clear, but later on, the tablet appeared dull, due to swelling of the tablet. The gastric retention is due to floating in the first few hours, and later, it is due to obstruction of the tablet at duodenum as seen in Fig. . The radiographic pictures of healthy volunteers confirm the in vivo
buoyancy in the stomach for 320
48.99 min (n
6). This gastric retention occurred due to swelling and floating characters of the dosage form.