Thermal sintering driven modulation of drug release and buoyancy characteristics in dasatinib gastro-retentive tablets

Aim: The present investigation deals with the formulation of floating-bioadhesive matrix tablets of verapamil hydrochloride (VH). The main objective of this work was to overcome the limitations of the conventional floating matrix tablets. Materials and Methods: Hydroxypropyl methylcellulose (HPMC) K15M was used as a matrix-forming agent whereas carboxymethyl tamarind gum (CMTG) was used to promote bioadhesion. Systematic optimization was performed using a central composite design with two independent variables and six dependent variables. Tablets were prepared by using the wet granulation method. The effect of polymer ratio (HPMC:CMTG) and sodium bicarbonate (SB) concentration on the total floating time (TFT), floating lag time (FLT), bioadhesion, swelling, and drug release (DR) was studied and optimized. Results and Discussion: Floating-bioadhesive matrix tablets of VH showed good physicochemical properties. The FLT was within the range of 2.87-14.41 min and TFT was more than 12 h. The tablets showed 17-30% of burst release in the 1st h and controlled release over a period of 12-h. DR and swelling were significantly (P < 0.05) affected by polymer ratio and concentration of SB in formulation. The polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P < 0.05). Optimized batch showed FLT of 6.14 min, bioadhesion of 17.23 g, swelling of 74.83% at 5 h, and DR of 75.48% at 10 h, with anomalous release mechanism. The observed values were near to the predicted values obtained by the experimental design. Conclusion: The floating-bioadhesive tablets of VH prepared using HPMC and CMTG exhibited a potential to retain and control the release of drug in stomach for more than 12 h and may be used as an alternative to the conventional floating tablets of VH.

The purpose of this research was to prepare a floating matrix tablet containing domperidone as a model drug. Polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) were evaluated for matrix-forming properties. A simplex lattice design was applied to systemically optimize the drug release profile. The amounts of PEO WSR 303, HPMC K15M and sodium bicarbonate were selected as independent variables and floating lag time, time required to release 50% of drug (t50) and 80% of drug (t80), diffusion coefficient (n) and release rate (k) as dependent variables. The amount of PEO and HPMC both had significant influence on the dependent variables. It was found that the content of PEO had dominating role as drug release controlling factor, but using suitable concentration of sodium bicarbonate, one can tailor the desired drug release from hydrophilic matrixes. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). The tablets of promising formulation were found to be stable for 3 months under accelerated (40°C / 75% RH) stability testing.

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers. Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour. Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT. Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

Floating matrix tablets were designed and evaluated. Theophylline was used as a model drug. The system was prepared by mixing drug, matrix-forming polymer (hydroxypropyl methylcellulose, HPMC) and fillers together. The blended powder was compressed by hydraulic press. The effect of formulation variables such as type of matrix forming polymer (HPMC K100LV, HPMC K4M, HPMC K100M), amount of effervescent agent (0, 20, 30, 40% w/w) and compression force (0.5, 1 ton) on floating properties and drug release of floating matrix tablets were investigated. The results demonstrated that type of polymer affected floating properties of the floating matrix tablets. The floating matrix tablets prepared from lower viscosity HPMC (HPMC K100LV) showed faster drug release than those prepared from higher viscosity HPMC (HPMC K4M, HPMC K100M). Increasing amount of effervescent agent decreased time to float and increased drug release from the floating matrix tablets. Higher compression force did not affect time to float but decreased drug release from the floating matrix tablets. According to these results, floating properties and drug release of the floating matrix tablets could be modified by formulation variables. Some floating tablet formulations developed in this study showed good floating properties (time to float less than 15 minutes, floating time more than 8 hours) with sustained release as required. The system is promising as a carrier for gastroretentive drug delivery systems.

Objective: To develop a Verapamil hydrochloride controlled release gastro-retentive (CRGR) tablet for once-daily dosing using the response surface Box-Behnken Design (BBD) approach for the improvement of bioavailability and reduction in dosing frequency to overcome the issues related to the conventional tablet formulation. Methods: For the optimization, 33Box-Behnken design was used. The independent variables were selected, the amount of Compritol 888 ATO (A), HPMC K15M (B), and Sodium bicarbonate (C). The dependent variables were Cumulative % drug release in 1.5 h (Q1.5), 8 h (Q8), 24 H (Q24) and floating lag time (FLT). Flow properties of pre-compressed powder, physical characteristics, drug content, floating lag time, total floating time and in vitro dissolution study of all formulation were assessed. In vitro dissolution study of optimized formulation that was prepared experimentally was performed and compared with predicted data obtained from the software. Drug release kinetics of the optimized formulation was also assessed to know the mechanism of drug release from the CRGR tablets. Results: Responses of experimental runs were found as Q1.5: 12.78-33.62 (%), Q8: 43.03-64 (%), Q24: 78.77 to 103.57 (%) and floating lag time as 3.01 min to 5.08 min. The predicted optimized formula with the highest desirability value of 0.963 containing amount 126.030 mg, 160.00 mg and 80.955 mg of Compritol 888 ATO, HPMC K15M and Sodium biarbonate respectively was prepared and evaluated. The experimental values from optimized formulation were obtained as Q1.5: 23.397%, Q8; 57.744%, Q24: 97.150% and FLT: 3.12 min. Predicted and experimental results were found comparable for all the responses. The release data from the optimized formulation were best fitted in the Higuchi (r2 = 0.999) and the Korsmeyer-Peppas ((r2 = 0.998, n=0.54) model. The in vitro drug release studies indicated that the Verapamil hydrochloride gastroretentive tablet releases the drug in controlled manner for 24 h. Conclusion: This study found that using Box-Behnken Design with the response and variable relation, it is possible to achieve an optimum formulation with desirable characteristics. This study also established the suitability of Compritol 888 ATO-HPMC K15M combination with Sodium bicarbonate to increase the gastric residence time tablet formulation had once-daily dosing of the Verapamil Hcl with improved bioavailability for effective management of hypertension.

The objective of this study was to develop the Verapamil hydrochloride sustained-release floating matrix tablets using gas-generation approach to prolong the gastric residence time. Floating tablets were prepared using hydroxypropyl methylcellulose K4M (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and Citric Acid as floating assistant agent. A 32 factorial design was used to select the optimized formulation wherein HPMC K4M (X1) and Citric Acid (X2) were taken as independent variables and Floating lag time (FLT), amount of drug release after 24hrs. (Q24) were taken as dependent variables. The release data were evaluated by the model-dependent (curve fitting) method using PCP Disso v2.08 software. Optimisation studies were carried out by using the Design Expert software (version 8.0.1). The floating tablets were evaluated for uniformity of weight, hardness, thickness, swelling index, friability, drug content, FLT, and in vitro release. The in vitro drug release followed Hixson-Crowell model and mechanism of drug release was found to be anomalous or non-fickian type. The optimized formulation was F3 containing HPMC K4M 15%, and Citric acid 3% having minimum FLT and maximum drug release after 24 hrs.

Objective: The present study aimed at designing of floating matrix tablet of clopidogrel bisulphate by design of experiments.Methods: The tablets were prepared by direct compression technique using hydroxypropyl methylcellulose K15 (HPMC) as a matrix polymer and sodium bicarbonate as a gas generating agent. In order to optimize the concentration of HPMC (X1) and sodium bicarbonate (X2), a 32 full factorial design was employed. The tablet formulations were evaluated for floating lag time (Y1), floating or buoyancy time (Y2), percent water uptake, and differential scanning calorimetry (DSC) and in vitro drug release (Y3).Results: The formulation variables, HPMC concentration, and sodium bicarbonate concentration exerted a significant effect on floating behavior and drug release characteristics of the tablet. The optimized formulation, with 15% sodium bicarbonate concentration and 30 % HPMC concentration resulted in 5±2.6 sec of floating lag time, 22.0±0.6 h of floating time and 42.0±0.99% of clopidogrel bisulphate release in 8 h of dissolution study. The drug release mechanism was identified as nonfickian. The water uptake studies revealed that with an increase in HPMC concentration, there was an increase in swelling index of tablet whereas higher sodium bicarbonate concentration supported the faster erosion of matrix tablets. DSC study revealed no interaction of drug and polymers. The lower percentage error between predicted and observed responses of the optimized formulation validated the design.Conclusion: The study demonstrated successful designing of floating clopidogrel bisulphate tablet with factorial design.

Background: The aim of the present study was to formulate and evaluate floating bioadhesive tablets of Nizatidine which is a competitive, reversible H2-receptor antagonist. Floatingbioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong gastric residence time was prepared. Methods: Polymers used were Hydroxy Propyl Methyl Cellulose (HPMC) K15M as matrix forming water swellable release retarding polymer and carbopol 934P as bioadhesive polymer. The gas generating agents used were sodium bicarbonate and citric acid. The prepared floating bioadhesive tablets of Nizatidine were optimized by 32 factorial design to study independent variable X1 (concentration of CP 934P) and X2 (concentration of HPMC K15M) and dependent variables as floating lag time, cumulative percentage drug release at 12h and swelling index. Tablets were evaluated for various parameters such as hardness, friability, drug content, swelling behavior, floating lag time, bioadhesive strength, drug release profile and stability. Results: All the formulations passed the test for weight variation, hardness, content uniformity and showed acceptable results with respect to drug content (97.93 ± 0.57) and % friability. The tablet containing 25% HPMC K15M and 13.75 % Carbopol 934P was selected as optimized formulation which showed the floating lag time of 74.34±2.08 seconds, drug release of 97.03±0.55% at 12 h (R12h,%), S.I as 79.24±0.87 at 9 h and bioadhesive strength as 10.0023±21.47 g. Stability of the formulation was proved using stability study. Conclusion: The formulated tablets have a potential for controlled release of the drug through floatation and bioadhesion.

Osmotic Pellet System Comprising Osmotic Core and In-Process Amorphized Drug in Polymer–Surfactant Layer for Controlled Delivery of Poorly Water-Soluble Drug

Objective: In the present research work, the aim was to prepare the bilayer tablet of atenolol for biphasic drug release to improve its bioavailability and absorption in the lower gastrointestinal tract. Methods: In the formulation of immediate release crospovidone, croscarmellose sodium, and sodium starch glycolate was used as super disintegrate and was directly compressed. For a sustained release portion different grade hydroxypropyl methylcellulose (HPMC) K4M, HPMC K15M, gum tragacanth, gum acacia, guar gum, and ethyl cellulose. Preformulation studies were performed before compression. The compressed bilayer tablets were evaluated for weight variation, dimension, hardness, friability, drug content, disintegration time, and in vitro drug release using USP dissolution apparatus type 2 (paddle). Results: The formulation IR3 showed 95% drug release in 30 min, and regression coefficient value (r2) value was found to be 0.994 suggesting first-order drug release kinetics. The F9 formulation using HPMC K15M and gum acacia (1:1) showed 91.20% drug release at the end of 12 h, and regression coefficient value (r2) was 0.992 suggesting zero-order drug release kinetics. Formulation IR3F9 showed faster drug release for bilayer tablet containing 5%w/w crospovidone in immediate release layer and HPMC and guar gum (1:1) in sustained release. Formulation IR3F9 showed swelling index 206%, floating lag time was found to be 2 min and total floating time up to 12 h. Conclusion: The formulation IR3F9 showed a faster drug release profile among the others in the preparation of the atenolol bilayer tablet. Hence, it was considered as an optimized formulation.

The aim of this investigation was to design and assess the gastric floating tablets of Atenolol using thermal sintering and investigate the effect of sintering on PEO polymer. Atenolol is an Antihypertensive with only 50 percent bioavailability due to poor absorption in lower GI tract. Gastro retentive Floating tablets were prepared to enhance the gastric retention time, to prolong the drug release. PEO which was selected as sintered polymer. Tablets were prepared by direct compression method .Formulated tablets were exposed to different temperatures (400C, 500C and 600C) at various time intervals( 1h ,2h ,3h and4h) in a hot air oven .Post compression parameters were evaluated like weight variation, hardness, friability, floating lag time and total floating time. The result of the investigation indicates sintering influenced the floating time and dissolution properties. Weight variation, friability and content uniformity values were within limits. Sintering time and temperature contributes to effectiveness of polymers in extending drug release. Reduction in floating lag time and increase in total floating time as well as release of drug was delayed. All sintered formulation have no interaction was found in FTIR, DSC studies. All sintered tablets followed zero order with nonfickian diffusion mechanism. This study helps the use of thermal sintering in preparation of floating tablets.

Gastroretentive drug delivery systems (GRDDS) are designed to prolong gastric residence time and enhance the bioavailability of drugs with a narrow absorption window. Floating drug delivery systems remain buoyant in gastric fluid by forming low-density matrices or through gas-generating mechanisms, allowing prolonged gastric retention. Mitiglinide, a short-acting insulin secretagogue used in the management of Type-2 diabetes mellitus, exhibits low oral bioavailability, a short biological half-life, and requires frequent dosing. The present study aimed to develop and evaluate gastroretentive floating matrix tablets of Mitiglinide to achieve sustained drug release and improved glycemic control. Floating tablets were prepared by the direct compression method using hydrophilic polymers such as HPMC (K4M and K15M), Carbopol 934P, and sodium alginate, along with sodium bicarbonate and citric acid as gas-generating agents. Nine formulations were developed by varying polymer concentrations and evaluated for pre-compression flow properties and post-compression quality parameters. Floating lag time, total floating time, and in-vitro drug release studies were conducted. The results demonstrated satisfactory flow properties, acceptable tablet characteristics, rapid buoyancy, prolonged floating time, and sustained drug release up to several hours. Drug release followed Higuchi diffusion kinetics, with increased polymer concentration resulting in slower release. The study concludes that gastroretentive floating matrix tablets of Mitiglinide are a promising approach for enhancing bioavailability and reducing dosing frequency in Type-2 diabetes management.

Many compounds with high aqueous solubility, limited absorption in the upper gastrointestinal tract, poor oral bioavailability, and pH-dependent chemical stability can benefit from sustained and gastric-specific delivery systems to improve oral absorption. Intragastric floating systems represent a promising strategy to address these challenges. However, their use is limited by factors such as long floating lag time (FLT), the reliance on high viscosity hydroxypropylmethyl cellulose (HPMC), complex formulations and non-biocompatible excipients. In this study, floating tablets were developed using different grades of HPMC, sodium alginate and sodium carboxymethylcellulose and a gas generating agent. The effects of formulation variables on the in vitro drug release, floating behavior, release mechanism and physical properties were evaluated. High viscosity HPMC 2208, when used as the predominant polymer, provided sustained drug release for up to 12h. However, it exhibited an excessively long FLT (> 6min), increasing the risk of premature gastric expulsion which could lead to incomplete absorption and reduced therapeutic efficacy. Incorporation of HPMC 2910 and increasing its proportion within the matrix gradually reduced FLT, enabling faster buoyancy while preserving sustained release characteristics. FLT could also be optimized by fine-tuning the content of sodium bicarbonate (NaHCO3). A higher NaHCO3 content resulted in shorter floating lag time and shifted the release mechanism towards matrix erosion.

Objective: To improve the treatment of H. pylori infection, by achieving the required bactericidal concentrations of antibiotics in the stomach, by delivering the antibiotics to the mucus layer and release the drug at the site of infection for a prolonged period would be significantly more effective than conventional dosage forms. Methods: The experimental method of the research was designed to prepare Levofloxacin floating by using Hydroxypropyl Methylcellulose (HPMC K4M), Hydroxypropyl Methylcellulose (HPMC K100M) and Xanthan gum by Three-level Box–Behnken design optimization method. The prepared tablets were evaluated for Thickness, Hardness, Friability, Weight variation, Swelling index (SI), Floating lag time (FLT) and Time required to release 90% of the drug from the tablet (T90%). Results: It was found that the Thickness-3.12±0.11 mm to 3.28±0.10 mm, Hardness-4.52±0.36 kg/cm2 to 4.81±0.24 kg/cm2, Friability-0.81±0.02g to 0.86±0.12g, Weight variation-480±1.90 mg to 523±0.89 mg, Swelling index (SI)-61.9±0.624% to 99.95±0.226%, Floating lag time (FLT)-81.12±0.63 s to 119.7±0.567 s and Time required to release 90% of the drug from the tablet (T90%)-7.0±0.55 h to 10.33±0.289 h. HPMC K100M and Xanthan gum showed good swelling as compared to HPMC K4M. The study revealed that HPMC K100M grade had a significant effect on drug release. Conclusion: The developed gastro-floating tablets can extend levofloxacin duration in the stomach and produce a prolonged release effect. The prepared levofloxacin floating tablet oral drug delivery system appears to be a promising choice for the efficient eradication of H. pylori

Piroxicam is an NSAID (non-steroidal anti-inflammatory drug) persisting antipyretic and analgesic effects and being usually implied in managing and treating osteoarthritis, rheumatoid arthritis, soft tissue disorders, ankylosing spondylitis, and acute gout and also in post-operative pain management. The present research was undertaken aiming to formulate Piroxicam encompassing floating oral in situ gels, in order to augment its anti-inflammatory activity and to alleviate its gastric ulceration potential. In the present work, a three-factor at two-level (23) factorial design was adopted to inspect the effects of three factors viz. sodium alginate [A], sodium bicarbonate [B], and sodium citrate [C] on the dependent variables like in vitro gelation, in vitro floating, percentage water uptake, and percentage drug release. All the formulations have exhibited pH ranging from 6.7 ± 0.25 to 7.4 ± 0.24. Percentage drug content was noted in the range of 96.3 ± 0.27 to 99.5 ± 0.28%. In vitro gelation was instantaneous post administration of the system, which remained intact for an extended time period. Percentage water uptake was in the range 9.01 ± 0.15 to 31.01 ± 0.25%; floating lag time was estimated around 7 ± 0.39 to 57 ± 0.36 s. Formulations F4 and F5 reflected floating even past 12 h. All the formulations have exhibited drug release of around 90% within 8 h. It was experiential that the chosen independent variables had significant effect on the dependent variables, justifying the robustness and aptness of design implied for optimization. The developed system may be a promising and alternative strategy to augment gastric retention of Piroxicam, thereby increasing its therapeutic efficacy. It even offers additional benefit of reducing the gastric irritation, tissue damage, and ulceration, by avoiding direct contact of drug with mucosa of stomach.