Core Tablets Research Articles

Development and evaluation of pulsatile drug delivery system of Telmisartan

The aim of the present study was the formulation of pulsatile tablets of Telmisartan by press coating technique that could release the drug time controlled manner. The core tablets and press coated pulsatile tablet of Telmisartan was prepared by direct compression technique. The core tablets were formulated using super disintegrating agent cross carmilose sodium and pulsatile tablets were by using polymer HPMC and Ethyl cellulose in various concentrations. Compatibility studies indicate that there is no interaction between the excipient and the drug. All tablets formulations were subjected to evaluation parameter. All the parameters were found within the limit. Pulsatile tablets formulation F3, F4 and F5 showed sufficient lag time of 4hr, 3hr and 4 hr respectively. The optimized formulation of F3 was consider as the best formulation with respect to drug content, hardness, lag time and In vitro drug release. Formulation F3 showed optimum lag time of 4 hour and release maximum drug in 8 hour. The developed formulation was found to be stable during the stability studies of 3 month indicating good stability of the tablets.

Formulation, Development and Evaluation of Pulsatile Tablets of Etoricoxib

Aim: This research aimed to develop a pulsatile drug delivery system (PDDS) for etoricoxib, selective COX-2 inhibitor analgesic, to address the limitations of conventional formulations by releasing the drug at specific intervals aligned with the circadian rhythm of pain. Method: Core tablets containing Etoricoxib were prepared by direct compression with varied concentrations of croscarmellose sodium as a superdisintegrant. The optimized core tablets were coated using hydrophilic (HPMC K4M) and hydrophobic (ethyl cellulose) polymers in different ratios to create press-coated pulsatile tablets with varying lag times. Physical properties hardness, thickness, friability, and disintegration, drug content uniformity, and in vitro release were evaluated. Results: The core tablets exhibited rapid drug release, with batch C3 showing 98.61% release within 60 minutes. Press-coated formulations with different polymer ratios exhibited varying lag times, with batch F3 achieving the optimal balance—providing a 4-hour lag time and 96.6% drug release over 8 hours. Stability studies confirmed the physical and chemical stability of the optimized formulation (F3) over 6 months under accelerated conditions. Conclusion: The developed press-coated pulsatile tablets of etoricoxib successfully achieved a controlled lag time and sustained drug release profile, making them suitable for chronopharmacological management of pain. Keywords: Etoricoxib, Pulsatile Drug Delivery System, Chronopharmacology, Press-Coated Tablets. etc

Understanding the effect of plasticizers in film coat materials on the physical stability of amorphous solid dispersions

Amorphous solid dispersions (ASDs) have been extensively utilized to improve the bioavailability of drugs that have low aqueous solubility. The influence of different excipients on the conversion of amorphous drugs into their crystalline forms in ASDs has been extensively researched. However, there is limited knowledge examining the impact of film coating materials on the physical stability of oral tablet formulations containing ASDs. In this study, we demonstrate that plasticizers present in film coats can have a detrimental impact on the physical stability of ASDs. We systematically compared two frequently used plasticizers in film coats: triacetin and polyethylene glycol 3350 (PEG 3350). To gain mechanistic insights into the detrimental effects of plasticizers on the physical stability of ASDs, plasticizer leaching studies and physical stability studies of solvent-evaporated and spray-dried intermediates (SDI) using two BCS class II drugs were conducted. Triacetin was found to leach into the tablet core within one week when stressed at 40°C/75% RH, whereas no leaching was observed for PEG 3350, as discerned from spectroscopic studies. We also found that triacetin-containing ASDs exhibited greater amorphous to crystalline form conversion of the drug compared to PEG 3350-containing ASDs after stability testing. Moreover, the incorporation of triacetin into polymers was found to cause a significant depression of glass transition temperature and upon equilibration with moisture, a drop below room temperature. Overall, these observations underscore the importance of carefully selecting plasticizers to be present in film coatings when developing ASD pharmaceutical products.

Design and Optimization of Ibuprofen and Ranitidine Hydrochloride TriLayer Tablets in Immediate Release Formulation by Quality by Design.

The current trend in pharmaceutical process development and optimization is known as quality by design (QbD). This methodical approach is founded on the concept that quality should be integrated into the product from the start, rather than assessed after manufacture. In this study, we demonstrate methods to improve the process parameters for making tri-layer tablets by applying QbD principles in a methodical way. Dependent elements with high to medium impact on the process. According to the study’s results, all systems showed signs of instant release. It appears that the structure of each formulation and the properties of the polymer utilized have a significant impact on the rate and mechanism of drug release. Substantial medication release is observed in the three-layer formulations. Both the pace and mechanism of drug release are significantly affected by the tablet’s geometrical features and structure, as well as the weight and thickness of the barrier layers. While data suggested that Fickian diffusion was primarily responsible for drug release in two-layer tablets, three-layer tablets showed signs of either anomalous diffusion or erosion/relaxation. Therefore, the drug was stabilized as immediate-release directly compressible triple layered Average core weight of tri-layered tablets (mg) was 1000 for ibuprofen, 100 for placebo and 200 for ranitidine, thickness (mm) was 9.00 ± 0.3, hardness (N) was 110 ± 25, core tablet weight was 1300.000 ± 2% mg and coated tablet weight was 1325 mg. Using other moisture-sensitive medications. This study provides the foundation for future research into optimizing the properties of tablets made by direct compression.

Scale-up of the film coating process using the example of vitamin and mineral complexes: from idea to process validation

Introduction. The development of defect-free film coating modes is an urgent task when transferring film-coated tablets technology. Technology transfer is an integral stage of the life cycle of any drug approved for industrial production. During the development of the technological process, deviations may occur, to eliminate which it is necessary to introduce auxiliary operations or change the chain of technological equipment.Aim. Optimize the process of applying a film coating to tablets of the core of the vitamin and mineral complex.Materials and methods. The objects of the study were biconvex core tablets in the form of a boat of a vitamin and mineral complex consisting of vitamins C + E + B1 and minerals. To ensure the required technological properties, auxiliary substances were used: microcrystalline cellulose, sodium croscarmellose, potato starch, calcium stearate, colloidal silicon dioxide. Ready-made film-forming mixtures (Colorcon®) in beige Opadry® II 85F 270000 were used as film-forming compositions. The film coating was applied in the craters with a perforated drum BG-80 (Pro-face, China) and BGK-150 (Zhejiang Canaan Technology Limited, China).Results and discussion. The process of applying a film coating to the core tablets of a vitamin and mineral complex has been studied. The analysis of the current technological chain showed a number of disadvantages – a large amount of manual labor, the need for matting the drum, the duration of the process, low loading, braking of the production cycle due to lagging at the stage of applying the film shell. To solve the discovered problems, a project was developed to scale the technology at the stage of applying a film shell to tablets-the cores of a vitamin and mineral complex. During the implementation of the process, new equipment was purchased and installed for production. The development of the technological process made it possible to multiply the one-time loading into the boiler (by 2–3 times), automate the process due to the automatic operation function according to the parameters set before the start of the technological process, and exclude the matting of the drum from preparatory work. The quality of film-coated tablets has improved, and the risk of defects has significantly decreased.Conclusion. During the study, it was proved that transferring the film coating process to another piece of equipment can improve the quality of the resulting film-coated tablets and optimize the technological process. A multiple increase in the loading size is not carried out at the same time by changing the number of nozzles and the inner section of the hose for applying the film coating material.

Formulation, Optimization, and Evaluation of Ezetimibe for Chronotherapeutic Drug Delivery using Compression-Coating Technology

Objectives: The purpose of the present study was to Formulation, optimization and evaluation of drug for chronotherapeutic drug delivery using compression coating technology for hypercholesterolemia. Material and Methods: The drug delivery system was designed to deliver the drug at a time when it could be needed for the most in the early morning (4 to 6 a.m.) for patients in case of hypercholesterolemia. The pulsatile concept was applied to the dosage form by having a lag phase followed by an immediate release. The prepared system consisted of two parts: a core tablet containing the active ingredient and fracture outer shell with delay-release polymer having diffusion characteristics. Solid dispersion was carried out by screening of betacyclodextrin, Polyvinyl pyrrolidone (PVP K30), and HPMC using three different drug complex ratios 1:1, 1:2, and 1:3 by a solvent evaporation method through spray dryer. The immediate-release core tablet (IRCT) was prepared by using a superdisintegrant with active ingredients. Screening of IRCT was carried out by pre and post compression parameters, disintegration time and an in-vitro dissolution study. The pulsatile release tablet (PRT) of optimized IRCT was made by Glyceryl Behenate and Dibasic Calcium Phosphate. Optimization of polymer concentration of PRT was carried out by pre and post-compression parameters, pulsatile lag time, and an in-vitro dissolution study. A 32 factorial design was employed to optimize the PRT. The design consisted of two dependent variables R1, and R2 independent variables X1 and X2. The two independent formulation variables selected for the study including Concentration of coating polymer and Concentration of lubricant. The dependent variables are Lag Time and Thickness. Results: XRD, DSC and FTIR spectra showed that solid dispersion was formed by the drug and PVP K30 complex. IRCT batch RR1 containing 22mg croscarmellose sodium to achieve good 30sec disintegration time and 98.34% drug release at the end of 20 minutes of Ezetimibe respectively. PRT formulation DR6 showed good pre and post-compression parameters with a satisfactory drug release of 98.34% for Ezetimibe respectively with a lag time of 6 hours. The 32 factorial design was used for the optimization of PRT parameters. A total of 9 experiments were performed for two factors at three levels each. The optimized batch showed 98.27% DR for Ezetimibe in 6.2 hrs (within 20 min after lag time) with pulsatile lag time up to 6.0 hrs and thickness of 5.10 kp. Conclusion: It was concluded that tablet within the tablet, pulsatile drug delivery of Ezetimibe (BCS class-II drugs) was successfully formulated with the advantage of enhanced solubility, and pulsatile release behavior and had an added benefit of suitable for chronopharmacotherapy of diseases that show circadian rhythms in their pathophysiology.

Impact of immediate release film coating on the disintegration process of tablets

Pharmaceutical tablets are often coated with a layer of polymeric material to protect the drug from environmental degradation, facilitate the packaging process, and enhance patient compliance. However, the detailed effects of such coating layers on drug release are not well understood. To investigate this, flat-faced pure microcrystalline cellulose tablets with a diameter of 13 mm and a thickness between 1.5 mm to 1.6 mm were directly compressed, and a film coating layer with a thickness of 80 μm to 120 μm was applied to one face of these tablets. This tablet geometry and immediate release film coating were chosen as a model system to understand how the film coating interacts with the tablet core. The coating hydration and dissolution process was studied using terahertz pulsed imaging, while optical coherence tomography was used to capture further details on the swelling process of the polymer in the coated tablet. The study investigated the film coating polymer dissolution process and found the gelling of dissolving polymer restricted the capillary liquid transport in the core. These findings can help predict the dissolution of film coating within the typical range of thickness (30 μm to 40 μm) and potentially be extended to understand modified release coating formulations.

Investigation of Groundnut Shell Powder as Potential Super Disintegrant in Chronotherapeutic Delivery of Sacubitril–valsartan

ABSTRACT Context: Chronotherapeutic delivery of antihypertensives plays a potential role in the treatment by providing a therapeutic amount of drug at the target site in the body. Sacubitril–valsartan (SV), an angiotensin receptor neprilysin inhibitor, has been indicated for the treatment of hypertension. The study explores the formulation and evaluation of compression-coated tablets (CCTs) of SV using a natural super disintegrant in the core tablet for chronotherapeutic drug delivery. Aim and Objective: The main objective of the current investigation is to study the applicability of groundnut shell powder (GSP) as super disintegrant and its role in chronotherapeutic drug delivery. Materials and Methods: Core tablets of SV were prepared using different concentrations of natural excipient (GSP) and compression coated. The CCT was evaluated for the postcompression tableting properties, in vitro drug release, Fourier transform infra red spectroscopy (FTIR), and stability studies and compared the disintegrating property with a synthetic excipient (crospovidone). Results: The results of the in vitro dissolution performance of core tablets indicated that the incorporation of GSP as a super disintegrant significantly reduced the disintegration time. Optimized core tablets were subjected to compression coating using a graded concentration of cellulose acetate phthalate as coating polymer and evaluated tableting properties and dissolution performance. Among all the formulations, CCT5 with 8% GSP in the core, coated with 300 mg coating polymer shown 6 h lag time followed by the rapid release of the drug within 1 h. Accelerated stability studies on optimized formulation revealed that there were no significant changes in the tableting parameters after storage indicating the stability of the formulation. Conclusion: The use of natural disintegrant in the core tablet offers a promising approach for rapid release of drug from CCT after a lag time of 6 h to achieve chronotherapy of SV.

Methacrylic acid grafted inulin and carboxymethyl cellulose as additives in the development of pH sensitive hydrogel matrix for colon targeting

AbstractCompression‐coated matrix tablets were developed to target budesonide (BUD) in the colonic region using methacrylic acid (MAA) grafted inulin (INU) and carboxymethyl cellulose (CMC). INU was grafted with MAA to impart anionic characteristics to the gum, making it feasible to form a hydrogel by cross‐linking with calcium gluconate (CG). The core matrix made up of MAA‐g‐INU alone disintegrated within 30 min and the core matrix made up of CMC alone completely released BUD within 6 h. The combination of MAA‐g‐INU and CMC produced a rigid matrix, which was able to completely release BUD after 7 h. Compression coating of the core tablets with MAA‐g‐INU and CMC did not release BUD in the first 4 h, and complete BUD release took place in the next 4 h. Compression coating led to the formation of a rigid and viscous gel layer outside the core matrices, which hindered BUD release. We conclude that compression coating with CG cross‐linked CMC and MAA‐g‐INU could be used as a matrix for colonic delivery of drugs.Highlights Compression coated matrices were developed for colonic delivery of BUD. The matrix retained drug release up to 4 h in upper gastrointestinal tract (GIT). The matrix exhibited complete drug release in the next 4 h in the colon.

OSMOTIC DRUG DELIVERY SYSTEM OF NICORANDIL: DESIGN AND EVALUATION

Objective: The purpose of the current research was to design a nicorandil formulation with controlled drug release using the principles of osmotic pump technology. Nicorandil is a biopharmaceutical classification system (BCS) class 3 drug, having a shorter plasma elimination half-life and bioavailability of 75 to 80%. Methods: The elementary osmotic pump (EOP) was prepared by coating a cellulose acetate polymer on the prepared core tablet. A 24-factorial design was applied to optimize the parameters for the osmotic tablet. A surface orifice was drilled. Results: Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) results showed that there was no interaction between drugs and excipients. A 24-factorial design was applied to optimize the parameters for the elementary osmotic pump. The optimized batch was characterized for in vitro drug release studies, and the effects of pH, osmotic pressure, and agitation intensity were analyzed. All the batches showed a drug release ranging from 90.48% to 98.78% after 12 hours. There was no change in the drug release pattern at different pHs and agitation intensities. The drug release was found to decrease with the increasing osmotic pressure of the dissolution medium. The results showed that the amounts of sodium chloride and mannitol were positively affecting the drug release, while the plasticizers PEG400 and DBP were not critical. Scanning electron microscopic studies (SEM) showed the integrity and surface morphology of the coating membrane before and after dissolution. The prepared EOP was found to deliver nicorandil at zero-order for up to 12 hours. Conclusion: Nicorandil was developed successfully as a controlled drug delivery during a 12-hour period, with variables optimized by the use of a 24-factorial design.

Tablet Shrouding Process Optimization with the Addition of Extended Fin to Improve Product Quality and Production Efficiency

In general, tablets are solid dose forms containing therapeutic substances, with or without fillers. Tablet compression is achieved by applying high pressure on powder (bulk) granules through a steel mold. The core tablet to be coated must meet certain standards because it will be moved and slammed repeatedly throughout the coating process. The extended fin is an additional fin that functions when the product is inserted into the coating pan and rotated, preventing the product from coming into direct contact with the coating pan wall during the coating process, resulting in friction and reactions that occur during the film coating process. For this reason, an expanded fin is inserted to reduce friction between the product and the pan coating machine's wall. The addition of the extended fin decreases friction between the drug and the machine wall, preventing the product coating process from reacting due to excessive friction with the machine wall. Additionally, the results of smoothness, glossiness, and color solidity are excellent. This resolves the issues that have previously lowered the proportion of production output.

Design of Colon Specific Delivery of Sulfasalazine Loaded Nanoparticles for Inflammatory Bowel Syndrome: Application of Experimental Design

Sulfasalazine is the first line treatment for Inflammatory Bowel syndrome. Conventional formulation have poor targeting properties for colon site.Therefore designof colon specific nanoparticles (NP) is an ideal for better therapeutic outcome. The study aims to formulate and evaluate polymeric Nanoparticles loaded with Sulfasalazine to target the colon. The nanoparticles were prepared by Nano-precipitation method using pH dependent polymer and the prepared nanoparticles were evaluated for FTIR, morphology, pH, Viscosity, Entrapment efficiency, particle size and zeta potential etc. The nanoparticles were used to formulate core tablet and core tablets were coated with Eudragit S100. The tablets were evaluated for hardness, friability, thickness, weight variation and In vitro release study. Totally six formulations were developed for preliminary trial with varying concentration of polymers. From the preliminary trial, code F2batch was found to be best formulation. The F2batch was fitted to central composite design with two independent factors i.e. Concentration of Eudragit S100 (X1) and polyvinyl alcohol (X2) with four dependent variables i.e. Entrapment efficiency -Y1; Hardness- Y2; Friability-Y3 and In-vitro drug release- Y4. The formulation (code R6) was found to be the optimizedformulation. The optimized colon targeted tablets provide satisfactory release and might be suitable for colon targeting of sulfasalazine with better therapeutic effect.

Formulation, In-vitro and In-vivo Evaluation of Chronology-based Mucoadhesive Drug Delivery System of an Antihypertensive Drug

Current research aimed to prepare and estimate chronology-based mucoadhesive PDDS of antihypertensive drug losartan potassium through formulation of fast-dissolving core tablet and incorporation of core tablet to polymer coating to formulate bioadhesive PDDS through direct compression system. The coating was done by using polymers ethyl cellulose and carbopol 934. Pre-compression and post-compression parameters, drug release, lag time and mucoadhesive examination was assessed for the formulation. The expected lag time for hypertension is 8 hours; hence, this lag time was achieved by using a bioadhesive pulsatile system. The optimized formulation showed 8 hours lag time with appropriate mucoadhesion for an equivalent period. Moreover, in-vitro as well as in-vivo mucoadhesion investigations reflected the positive outcomes. Consequently, the BPDDS was the finest preventative substitute for drugs with the highest absorption in the stomach and for drugs used to treat diseases related to circadian rhythm

Bioavailability Study of Experimental Push–pull Osmotic Pump Tablet of Nifedipine in Dogs

This study aimed to assess the bioavailability of experimental extended-release nifedipine tablets of push-pull osmotic pump type composed of a semipermeable membrane-coated bilayer core tablet containing PEO N10 and PEO 303 in drug layer and push layer, respectively on dogs. A test on dogs was performed using a two-way randomized crossover design with a single oral dose, fasting condition. Plasma samples were obtained at intervals and analyzed for nifedipine by UPLC-MS/MS after liquid-liquid extraction using glibenclamide as the internal standard. The pharmacokinetic parameters were calculated and the bioavailability of nifedipine extended-release tablets was evaluated by comparing the pharmacokinetic parameters between the prepared extended-release tablets of 30 mg NIF and the reference tablets of Adalat LA 30 mg. It was found that the prepared push-pull osmotic pump tablets of 30 mg nifedipine were equivalent in bioavailability to Adalat LA reference tablets of 30 mg nifedipine in experimental dogs according to the regulations of US-FDA and Vietnamese pharmacopeia 5th edition. The main pharmacokinetic parameters of nifedipine test and reference tablets after a single oral administration were as follows: Cmax 26.95 ± 7.82 (ng.mL-1) and 27.20 ± 6.99 (ng.mL-1), Tmax 12.33 ± 3.44 hours and 11.50 ± 3.33 hours, AUC0-96 728.96 ± 328.87 (ng.h.mL-1) and 702.48 ± 404.48 (ng.h.mL-1), AUC0-∞, 741.05 ± 340.39 (ng.h.mL-1) and 710.71 ± 408.76 (ng.h.mL-1), MRT 21.80 ± 5.25 hours and 22.06 ± 5.20 hours, respectively. The 90% confidence intervals for the ratio of Cmax, AUC0-∞, and MRT values for the test and reference products, using logarithmically transformed data were 90.82% - 108.09%, 91.97% - 118.21%, 90.74% -107.62%, respectively. No statistically significant difference was found for the Tmax value.

Selection of excipients for the formulation of varenicline tablet cores

The active pharmaceutical ingredient (APS) of varenicline is a tartrate with the chemical name 7,8,9,10‑Tetrahydro-6,10‑Methano-6H-pyrazino(2,3‑h) (3)benzazepine (as tartrate). Varenicline free base is an achiral molecule, however varenicline tartrate, which is formed by the reaction of varenicline free base and L-tartaric acid, is optically active and has an absolute counterion configuration of 2R, 3R. At the moment, only the drug Champix, produced by the pharmaceutical company Pfizer, is represented among direct analogues, so the development of a domestic analogue is an urgent topic of research. The purpose is to develop the optimal composition of varenicline tablet cores to create a finished dosage form.

Development of Pharmaceutical Equivalent Montelukast Sodium Immediate-Release, Film-Coated Tablets

Montelukast tablets are sold under the brand name Singulair and are used to control and prevent asthma symptoms. In this study, 10 mg film-coated montelukast tablets were developed as a generic drug in order to evaluate the pharmaceutical equivalent of the innovator’s products. The primary formulation ingredients used in all developed formulations (F1-F5) were the same as those described in the Singulair tablet package insert, except for formulations F3, F4, and F5, to which solubilizing enhancers were added to increase montelukast solubility. The core tablets were produced using the wet granulation method before being coated with HPMC polymer. FT-IR and DSC were used to determine drug and excipient compatibility. The micromeritic properties of the granules were assessed. The physicochemical properties of generated montelukast tablets and Singulair tablets were also investigated. The dissolution profiles of the tested drug and the innovator were assessed in a variety of pH mediums (pH 1.2, 4.5, 6.8, and water). The similarity (f2) and difference (f1) factors were computed. The accelerated and long-term stability of the tested drug in hot and humid climate zones was evaluated. The analytical method validation used in this study was ICH-acceptable for 8 parameters including specificity, range, linearity, accuracy, precision, limit of detection, limit of quantitation, and robustness. F1-F5 granules had similar properties, such as a pale-yellow color and excellent flow properties. There were no chemical interactions between montelukast and the excipients according to FT-IR and DSC analyses. The physical properties of all developed montelukast film-coated tablets were similar (average weight 212-218 mg; thickness 3.02-3.07 mm; assay 101-102% LA; disintegration time 3-4 min), except that the disintegration time of F3 was 8.10 min and that of F5 was 5.90 min, which was caused by the addition of poloxamer 188 to the formulation. In all mediums, only the F1 formula produced acceptable comparison dissolution profiles to Singulair. After 6 months of storage under accelerated and long-term conditions, the results showed the F1 formulation remained physically and chemically stable.

Extending the Use of Optical Coherence Tomography to Scattering Coatings Containing Pigments

Coating thickness is a critical quality attribute of many coated tablets. Functional coatings ensure correct drug release kinetics or protection from light, while non-functional coatings are generally applied for cosmetic reasons. Traditionally, coating thickness is assessed indirectly via offline methods, such as weight gain or diameter growth. In the past decade, several methods, including optical coherence tomography (OCT) and Raman spectroscopy, have emerged to perform in-line measurements of various subclasses of coating formulations. However, there are some obstacles. For example, when using OCT, a major challenge is scattering pigments, such as titanium dioxide and iron oxide, which make the interface between the coating and the tablet core difficult to detect. This work explores novel OCT image evaluation techniques using unsupervised machine learning to compute image metrics. Certain image metrics of highly scattering coatings are correlated with the tablet thickness, and hence indirectly with the coating thickness. The method was demonstrated using a titanium dioxide rich coating formulation. The results are expected to be applicable to other scattering coatings and will significantly broaden the applicability of OCT to at-line and in-line coating thickness measurements of a much larger class of coating formulations.

Assessment of the Opacity of Titanium Dioxide Free Film Coating Formulations

Titanium dioxide (TiO2) iswidely used as an excipient in pharmaceutical film coating formulations. InAugust 2022, the European commission (EC)adopted a ban on the use of TiO2 (E171) as a food additive.There is uncertainty around the implications of this decisionon pharmaceutical products, and a potential need to find suitable alternativesto TiO2. Inthis study, we evaluated the opacity of the different TF film coating systemsby assessing the ability of TF film coatings tomask coloured tablet cores at varying weight gains.HPMC-based film coatings containing CaCO3 demonstratedthe best covering potential and were positively correlated to the amount ofCaCO3 present, while PVA-based film coatings containing CaCO3showed poor coverage, even at 9% weight gain. 

Design, Optimization and In vitro Evaluation of Mesalazine 400 mg Delayed Release Tablet for Colon Specific Delivery

Ulcerative colitis is a chronic inflammatory disease, and patients would get benefit more if the drug is given directly to the colon. Mesalazine is intended to deliver to the colon for treating ulcerative colitis. Here, we aimed to design and optimize mesalazine 400 mg delayed release tablet for colon-specific delivery using a quality by design (QbD) approach. The tablet was first formulated as an optimized core tablet and then coated with Eudragit S 12.5 for ensuring colonic delivery. The experimental design for the core tablet was constructed using a 32 full factorial design, where the percentages of sodium starch glycolate (SSG) and polyvinylpyrrolidone (PVP K-30) were independent variables and the tablet hardness (kg/cm2) and cumulative percentage of drug release at pH 7.2 phosphate buffer after 1.5 hours were treated as responses. Responses obtained from the initial exploratory formulations were evaluated to develop an optimized formulation to have a hardness value of 7-8 kg/cm2 and the maximum amount of drug release at pH 7.2 buffer. The optimized formulation involved the use of SSG and PVP K-30 at 3.05% and 1.69%, respectively. Hardness and cumulative percent of drug release obtained for the optimized core tablet were 7.8 kg/cm2 and 91.76%, respectively. The compatibility of drug and excipients was studied utilizing XRD, FTIR and TGA. The optimized core tablet was then coated with Eudragit S 12.5 to deliver the drug selectively to the colon and further assessed for its in vitro dissolution. Dissolution studies indicated that coated tablets with a weight gain of 7.4% exhibited the maximum cumulative percent of drug release (91.19 ± 0.11%), with a zero-order drug release profile (R2 = 0.943). A stability study performed according to ICH Q1A (R2) guidelines at accelerated storage conditions identified that there was no significant change in drug content over the storage period, indicating the stability of the formulated tablet batches. Together, these data suggest that the mesalazine tablet developed through the QbD approach offers excellent physical properties and drug release profile and, therefore, could be recommended for commercial manufacturing. Dhaka Univ. J. Pharm. Sci. 22(2): 189-201, 2023 (December)

Physicochemical Characterization and Reverse Engineering of Reference Market Product for Generic Formulation Development

The present study aimed to carry out reverse engineering of reference innovator product (Xarelto® 20 mg film-coated tablets) to decode the critical scientific information that is needed for successfully develop a stable and bio-equivalent generic formulation of rivaroxaban 20 mg film-coated tablets. The innovator product characterization was done followed by deformulation of the reference product (Xarelto® 20 mg film-coated tablets) to quantity critical excipients to decode the innovator product’s quantitative composition and to identify the manufacturing process used to manufacture the innovator product. The particle size distribution and particle size distribution of rivaroxaban API used in the innovator product were performed using hot-stage microscopy. The polymorphic form of rivaroxaban API used was identified using DSC and XRD methods. Visual, tactile and microscopic evaluation of granules obtained from crushed tablets of the innovator product revealed that the granulation process was used in the manufacturing of the innovator product. It was further concluded that the manufacturing process is wet granulation process due to the presence of organic solvent in the innovator core tablet. Physical evaluation was done to know the tablet weight, shape, size, coating appearance, tablet hardness and disintegration time. Chemical analysis was performed to record the drug content, percentage impurity and dissolution profile. The decoded information can serve as a reference for a faster and bioequivalent generic formulation development with reduced cost, time, effort, and a higher success rate