FIXED-DOSE COMBINATION DRUGS AS TABLET IN TABLET: A REVIEW

The Pharmaceutical industry has become more interested in developing fixed-dose combinations (FDCs) in recent years. FDCs have been used successfully in a variety of clinical areas, including diabetes, HIV/AIDS,and cardiovascular diseases etc. FDCs are intended to extend the product life cycle and enhance patient compliance by decreasing cost. Active Pharmaceutical ingredients are chosen for FDC development based on variety of purposes such as Pharmacokinetic profile, drug-drug interactions, mechanism of action, and manufacturability for successful development. Tablet in tablet technology has gained popularity in recent years for creating modified release products. The compression coating or solvent-free-coating technology is also known as Tablet in Tablet technology. Tablet in Tablet technology is presently the finest alternative technology for the formulation of bilayer tablets for physical separation of active medicines and used to avoid chemical incompatibilities and to produce different drug release patterns such as rapid release, sustained release, controlled release, delayed release, and pulsatile release. This review mainly focuses on combining the techniques of both FDC and Tablet in Tablet formulations which offer a wide variety of benefits such as increased patient compliance, convenience, separation of incompatible ingredients, avoiding close interaction of two drugs, achieving various drug release patterns and maximizing the potency of both drugs over conventional oral dosage forms Keywords: Fixed dose combinations, Tablet in tablet technology, Compression coated tablet, Bilayer tablet, delayed release

Design and Evaluation of Press Coated Formulation of Aceclofenac and Comparison with Marketed Preparations.

The primary objective of the studies is to investigate whether compression coating could be used to produce tablets providing maximum drug plasma concentration 6 to 8 hours after an evening dose taken at approximately 22:00. Fast Dispersible core tablets containing Aceclofenac were prepared using super disintegrants like Ac-Di-Sol, Crospovidone, and Sodium starch glycolate through wet granulation method and evaluated for various parameters. Prepared press-coated tablets were characterized for physical parameters, drug content, lag time, in vitro drug release characteristics. Aceclofenac formulation tablets of batch F4 containing combination Methocel K4M and Methocel K100M showed desired lag time along with drug release as compared to other formulations. The Comparative dissolution study of an optimized formulation containing Aceclofenac was carried with marketed preparations also showed good results.

Preparation and Evaluation of Zafirlukast Compression Coated Tablets for Chronotherapeutic Drug Delivery

The objective of the present study was to formulate and evaluate an oral, time-controlled drug delivery system of Zafirlukast. Zafirlukast belongs to BCS class II drugs as it has poor aqueous solubility and good permeability. Hence an attempt has been made to improve its aqueous solubility by solid dispersion technique so that its dissolution, bioavailability, and therapeutic effect can be optimized. The optimized solid dispersion was then formulated into a chronotherapeutic drug delivery system by compression coating technology. FT-IR study revealed that there was no chemical interaction between the drug and polymers used. Tablets were prepared by direct compression method using different super disintegrants and then followed by compression coating using natural polymers. Pre-compression and post-compression parameters complied with the Pharmacopoeia limit for the tablets. In vitro release studies were performed and the results indicated the formulation Z9F9 to be the optimized formulation.

FORMULATION AND IN VITRO EVALUATION OF RAMELTEON TABLETS FOR COLON DRUG DELIVERY SYSTEM BY COMPRESSION COATING

Objective: Ramelteon, is a sleep agent that selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN), instead of binding to GABAA receptors. In the present research work, the formulation of ramelteon targeted to colon by using various polymers developed. Methods: Colon-targeted tablets were prepared in two steps. Initially, core tablets were prepared and then the tablets were coated by using different pH dependent polymers. Ethylcellulose, Eudragit RLPO and L100 were used as enteric coating polymers. The precompression blend of all formulations was subjected to various flow property tests and all the formulations were passed the tests. The tablets were coated by using polymers and the coated tablets were subjected to physical characterization, drug content, in vitro drug release and kinetics of drug release. Results: Among all the formulations, F4 formulation was found to be optimized as it was retarded the drug release up to 18 h and showed maximum of 99.25% drug release. It followed the first-order kinetics mechanism. All the formulations having Korsmeyer-Peppas ‘n’ values are in the range of 0.540 to 0.818. Hence, it was concluded that the prepared formulations followed non-Fickian diffusion. Conclusion: An effective and stable remelteon colon targeted formulation developed for treating insomnia.

Development and Evaluation of Mucoadhesive Tablets of Cinnarizine Using Carboxymethylated Guar Gum by Compression Coating Technique

The e study was designed to perform carboxymethylation of guar gum and to develop mucoadhesive tablets of cinnarizine by compression coating technology. Carboxymethyl guar gum was synthesized and characterized by FTIR, SEM, XRD and DSC techniques. Inner core tablets of cinnarizine were compression coated with guar gum and carboxymethylated guar gum. The formulated mucoadhesive tablets were evaluated for various tablet parametric tests viz. hardness, friability, content uniformity, thickness. Ex vivo mucoadhesion strength and in vitro drug release studies were also conducted. Appearance of new FTIR peaks, surface morphology analysis by SEM, reduction in crystallinity by XRD and appearance of the endothermic peak in DSC thermogram point out towards successful carboxymethylation of guar gum. Mucoadhesive strength of F1CGG to F4CGG batches of mucoadhesive tablets prepared with carboxymethyl guar gum found higher than F1GG to F4GG batches of tablets prepared with guar gum. Carboxymethyl guar gum exhibited sustained release effect on in vitro release cinnarizine from compression coated mucoadhesive tablets. The study confirms that carboxymethylation of guar gum improves the mucoadhesive properties of pure guar gum. Also, the compression coating of carboxymethylated guar gum enhances the gastric retention time and sustained release of cinnarizine. Carboxymethyl guar gum can be used as mucoadhesive polymer for developing different mucoadhesive drug delivery systems.

Review on Tablet in Tablet techniques

Background Among all available dosage form, tablet is most widely used because of its stability and patient acceptability. The better aesthetic quality like color, texture, mouth feel, and taste masking depended on film and sugar coatings, so the coating is an important part in the formulation of the tablet. The present work aims to comprehensively review the formulation, characterization, and challenges in the development of Tablet in Tablet dosage form. Main text Film and sugar coatings have the number of disadvantages; most important one is the utilization of aqueous or organic solvent that leads to toxicity. To overcome this problem in the year 1896, Noyes firstly introduced the compression coating or Tablet in Tablet technique. In the development of Tablet in Tablet dosage form, substantial attention among researchers and various research reports and patents inputs can be found in the literature. Also, we focused on the recent advancements in techniques like one-step dry-coating (OSDrC®) for manufacturing Tablet in Tablet dosage form. Conclusion The current review gathered information on the latest patent, formulation, advantages, and disadvantages of Tablet in Tablet or compression coating. The review also elaborates on the importance of Tablet in Tablet techniques in the development of a modified release system. Graphical abstract

FORMULATION AND EVALUATION OF COMPRESSION COATING FLOATING TABLETS OF CARVEDILOL PHOSPHATE ONCE DAILY DOSE

Objective: The rationale for the study was to develop a once-daily dose of immediate as well as a gastro-retentive form of carvedilol phosphate by compression coating floating technique.Methods: In the presented study the core tablet was containing half the quantity of the drug formulated as floating drug delivery using different controlled release polymers blend in various proportions like ethyl cellulose, carbopol, hydroxypropyl methylcellulose (HPMC) K4, K15, and K100 by direct compression method. Outer coat layer was formulated with rest of the drug with the blend of different super disintegrants in various proportions like crospovidone, croscarmellose sodium (CCS), sodium starch glycolate (SSG) for the immediate release of the drug. Both the immediate and controlled formulation was separately formulated from sf1 to sf9 and f1 to f9 respectively. Based on the evaluation parameters finally, formulation F1 to F9 were formulated by applying compression coating floating method. These formulations were characterized for their tablet density, disintegration time, floating lag time, in vitro drug release, drug-excipients interaction and accelerated stability studies etc.Results: The result revealed formulation sf9 containing SSG of 15% was able to 97.2% of drug release within 15 min towards the achievement of immediate release. Similarly, the formulation f9 containing 0.5:0.5:4.5 ratios of ethyl cellulose, carbopol and HPMC K15 was able to 95.3% of drug release within 16h. From compressed coat tablets batches of F1 to F9, based on the dissolution data F9 was considered as an optimized formulation which was able to release 48.6% of drug release within 15 min and cumulatively controlled the release up to 96.4% for 16 h, followed zero-order kinetics and Higuchi pattern.Conclusion: The results obtained in this research work clearly indicated that the compression coating floating tablet of carvedilol phosphate was the best dosage form for the treatment of hypertension. Results of the evaluation of prepared batches indicate that the batch F9 is a promising formulation for both a quick onset of action as well as gastro-retentive dosage form to maintain the constant drug action which would improve the maximum therapeutic efficacy and patient compliance.