Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride

Abstract

Ranitidine HCl, a selective, competitive histamine H2-receptor antagonist with a short biological half-life, low bioavailability and narrow absorption window, is an ideal candidate for gastro-retentive drug delivery system (GRDDS). Controlled release with an optimum retentive formulation in the upper stomach would be an ideal formulation for this drug. The aim of the present study was therefore to develop, formulate and optimize floating, bioadhesive, and swellable matrix tablets of ranitidine HCl. The matrix tablets were prepared using a combination of hydroxypropyl methylcellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC) as release retarding polymers, sodium bicarbonate (NaHCO3) as gas generating agent and microcrystalline cellulose (MCC) as direct compression diluent. Central composite design (CCD) was used to optimize the formulation and a total of thirteen formulations were prepared. Concentration of HPMC/NaCMC (3:1) (X1) and NaHCO3 (X2) were selected as independent variables; and floating lag time (Y1), bioadhesive strength (Y2), swelling index at 12 h (Y3), cumulative drug release at 1 h (Y4), time to 50% drug release (t50%) (Y5) and cumulative drug release at 12 h (Y6) were taken as the response variables. The optimized batch showed floating lag time of 5.09 sec, bioadhesive strength of 29.69 g, swelling index of 315.04% at 12 h, t50% of 3.86 h and drug release of 24.21% and 93.65% at 1h and 12 h, respectively, with anomalous release mechanism. The results indicate that sustained release matrix tablet of ranitidine HCl with combined floating, bioadhesive and swelling gastro-retentive properties can be considered as a strategy to overcome the low bioavailability and in vivo variation associated with the conventional ranitidine HCl tablet.

Pharmacokinetics and Food Effect Between a 100‐mg Sustained‐Release Tablet and a 50‐mg Immediate‐Release Tablet of Vildagliptin in Healthy Subjects

“…5 However, the modified-release formulations of the drug can be influenced by a combination of various factors after food ingestion, including dissolution, gastric emptying time, and gastrointestinal transition time. [16][17][18] In this study, the new SR formulation presented similar PK parameters such as T max , C max , and AUC 0-24h , regardless of food intake.…”

Preparation and Characterization of Hydrophilic Polymer Based Sustained-Release Matrix Tablets of a High Dose Hydrophobic Drug

“…The drug is dissolved by the penetrating dissolution media and diffuses from the swollen matrix. The rate of drug diffusion is controlled by the drug’s solubility in dissolution media, the micro-environment of the matrix, and the thickness of the diffusion layer [ 12 ]. Furthermore, drug release increases with the increase in the rate of erosion of the polymeric matrix.…”

“…Similarly, water-soluble excipients present in matrix tablets dissolve earlier and micro-channels are developed, which increase water penetration into the core of the matrix and increase the dissolution rate. A number of studies have reported an increase in the dissolution rate by increasing the quantity of lactose (a water-soluble excipient) in the matrix tablets [ 12 ], and a decrease in the dissolution rate with the inclusion of di-basic calcium phosphate (a water-insoluble excipient) [ 13 ]. Changes in the GIT conditions can also affect the mechanism of the dissolution rate due to enzymatic activity and variation in pH of the medium from highly acidic to alkaline.…”

Influence of Prunus domestica gum on the release profiles of propranolol HCl floating tablets

“…However, the formulation F1 showed the highest swelling index 77.23 ± 1.722% (2 hours) to 139.66 ± 1.44% (12 hours) and formulation F4 showed the lowest swelling index 59.87 ± 1.28% (2 hours) to 110.76 ± 1.33% (12 hours) respectively. Again the concentration of polymers appeared to be directly related to the swelling of the tablets [20,40].…”

“…The behavior in drug release might be due to the high concentration of polymer in the formulation which formed a strong gel layer around the tablet and thus made the diffusion layer stronger that consequently resulting in a slower release rate. This leads to slow erosion and hindrance in the diffusion of API from matrix tablets (Nigusse et al, 2021). It has been revealed that the formulation F4, containing a lower amount of polymer and gum, showed the initial burst release of Propranolol HCl.…”