In this present research work, the aim was to develop ileo-colonic targeted matrix-mini-tablets-filled capsule system of Naproxen for chronotherapeutic treatment of Rheumatoid Arthritis. So Matrix-mini-tablets of Naproxen were prepared using microsomal enzyme dependent and pH-sensitive polymers by direct compression method which were further filled into an empty HPMC capsule. The compatibility was assessed using FT-IR and DSC studies for pure drug, polymers and their physical mixtures. The prepared batches were subjected to physicochemical studies, drug content estimation, in-vitro drug release and stability studies. When FTIR and DSC studies were performed, it was found that there was no interaction between Naproxen and polymers used. The physicochemical properties of all the prepared matrix-mini-tablets batches were found to be in limits. The drug content percentage in the optimized formulation F18 was found to be 99.24 ± 0.10%. Our optimized matrix-mini-tablets-filled-capsule formulation F18 releases Naproxen after a lag time of 2.45 ± 0.97 h and 27.30 ± 0.86%, 92.59 ± 0.47%, 99.38 ± 0.69% at the end of 5, 8, 12 h respectively. This formulation was also found to be stable as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Thus, a novel ileo-colonic targeted delivery system of Naproxen was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis.

Pulsatile Drug Delivery Systems are gaining a lot of interest as they deliver the drug at the right place at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. Pulsatile Drug Delivery systems (PDDS) are basically time-controlled drug delivery systems in which the system controls the lag time independent of environmental factors like pH, enzymes, gastro-intestinal motility, etc. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release of the drugs is where a constant drug release is not desired. A pulse has to be designed in such a way that a complete and rapid drug release is achieved after the lag time. Various systems like capsular systems, osmotic systems, single and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. These systems are beneficial for the drugs having chronopharmacological behavior where night time dosing is required, such as anti-arhythmic and anti-asthmatic. Some of the disease conditions wherein PDDS are promising include duodenal ulcer, cardiovascular diseases, arthritis, asthma, diabetes, neurological disorder, cancer, hypertension and hypercholesterolemia. PDDS can be classified into time controlled systems wherein the drug release is controlled primarily by the delivery system, stimuli induced PDDS in which release is controlled by the stimuli, such as the pH or enzymes present in the intestinal tract or enzymes present in the drug delivery system and externally regulated system where release is programmed by external stimuli like magnetism, ultrasound, electrical effect and irradiation. Current review article discussed the reasons for development of pulsatile drug delivery system, types of the disease in which pulsatile release is required, classification, advantages, limitation, and Polymers used in pulsatile drug delivery system. To introduce the concept of chronotherapeutics, it is important to define the following concepts

Carbamazepine, a dibenzapine derivative with structure resembling that of tricyclic antidepressants, is used in the treatment of epilepsy. The major problem of this drug is very low solubility in biological fluids and poor bioavailability after oral administration. Carbamazepine fast dissolving tablets (FDT) have been prepared by direct compression method. Effects of superdisintegrants (such as croscarmellose sodium, crospovidone and sodium starch glycolate) on wetting time, disintegrating time, drug content, in vitro release, and stability parameters have been studied. The prepared tablets were characterized by DSC and FTIR Studies. No chemical interaction between drug and excipients was confirmed by DSC and FTIR studies. Disintegration time and dissolution parameters (t50% and t90%) decreased with increase in the level of croscarmellose sodium and crosspovidone, whereas disintegration time and dissolution parameters increased with increase in the level of the sodium starch glycolate in tablets. Among all formulations f8 was considered best. The results concluded that fast dissolving tablets of poorly soluble drug carbamazepine, showing enhanced dissolution, will lead to improved bioavailability, improved effectiveness and hence better patient compliance.

This research work aims to determine the pharmacokinetic parameters and in vitro-in vivo correlation of the selected ileocolonic-targeted coated mini-tablet filled capsule formulation of naproxen. The pure suspension and coated mini-tablet filled capsule formulation of naproxen were administered to adult albino rabbits through the oral route. The samples were analyzed for naproxen by an HPLC method. For the pure drug suspension, the peak plasma concentration was found as 8.499±0.029 μg/ml at 1.139±0.010 hours and the half-life was found to be 9.459±0.387 hours, whereas for the formulation the peak plasma concentration was found as 6.814±0.037 μg/ml at 8.042±0.069 hours and the half-life was found to be 19.657±0.359 hours. This decreased the peak plasma concentration at a delayed time and increased the half-life of the capsule formulation in comparison with the pure drug suspension which showed that naproxen was only targeted to the ileocolonic region. A significant in vitro-in vivo correlation (i.e. R2=0.9901) was also obtained. Thus, the results of these findings suggest that naproxen formulated as coated mini-tablets can be suitable for targeted ileocolonic drug delivery.

During the last few decades, pharmaceutical industry gave more importance to the controlled release of dosage forms like solid formulation, semi solid formulation, and topicalpreparation dueto efficacy and patient compliance. Normal topical preparations have some disadvantages like unpleasant odour, greasiness, and skin irritation reported in study cases. Also many topicalpreparations fail to reach the systemic circulation in sufficient amounts in few cases. This problem is achieved by the present formulation as microsponge in the areas of research. MDS is amicroscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microspongehaving particle size of 10-25 microns in diameter, have wide range of entrapmentof various ingredients in a single microsponges system and release them at desired rates.Microsponge is recent novel technique for control release and targetspecific drug delivery system. Microsponges are polymeric delivery system composed of porous microspheres. They are tiny sponge-like sphericalparticle with a large porous surface.Drug release in microsponge is done by the external stimuli like (pH, temperature, rubbing). It hasseveral advantageous over the other topical preparations are non allergenic, non toxic, non irritant, non mutagenic. Microsponges are designed to deliver apharmaceutical active ingredient efficiently at the minimum dose and alsoto enhance stability, reduce side effects and modify drug release.©2022iGlobal Research and PublishingFoundation. All rights reserved.