N. G. Raghavendra Rao

Enalapril maleate is the maleate salt of enalapril, a derivative of two amino acid, L-alanine and L-proline. Enalapril maleate is angiotensin converting enzyme (ACE) inhibitor. It lowers blood pressure by reducing peripheral vascular resistance without relatively increasing cardiac output, rate or contractility. All grades of essential hypertension especially in patients with diabetes and other chronic renal diseases like glomerulosclerosis can be treated with Enalapril. It is also indicated in the treatment of heart failure. Enalapril maleate is having a half life of 11 hrs. The bioavailability of Enalapril maleate tablets is approximately 55 % and food does not affect absorption. Hence, an attempt was made for preparations of a FDT of enalapril maleate were formulated by direct compression technique using co-processed superdisintegrant like Crospovidone and Croscarmellose sodium in different ratios. The prepared were evaluated for various pharmaceutical characteristics viz. hardness, % friability, weight variation, drug content, in-vitro dissolution profiles. Results showed that the direct compression technique by using co-processed superdisintegrants successfully used for enhancing the solubility of Enalapril Maleate. The prepared tablets were characterized using FTIR and finally the prepared tablets were evaluated for various pharmaceutical characteristics such as hardness, % friability, weight variation, drug content all the results were within the I.P Limit. Crosspovidone and CCS containing tablets rapidly exhibit high capillary activity and pronounced hydration with a little tendency to gel formation and disintegrate the tablet rapidly. The formulations prepared by co-processed superdisintegrants showed rapid % drug release due to fast disintegration of tablets. The formulation PM 3 and CP 6 shows 99% drug released within 20 minutes. The results of stability studies revealed no change in physical appearance, hardness, drug content and in vitro dissolution profiles, thus indicating that formulation was stable. Thus Results showed that the direct compression technique by using co-processed superdisintegrants successfully used for enhancing the solubility of Enalapril maleate.

The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The aim of writing this review on gastro retentive and floating drug delivery system was to compile the new literature with the principle mechanism of floatation to acquired gastric retention. The methodologies used in the development of FDDS by formulating effervescent and non effervescent floating tablets based on buoyancy mechanism. FDDS are of particular interest for drugs that are locally active and have narrow absorption window in stomach or upper small intestine, unstable in the intestinal or colonic environment, and exhibit low solubility at high pH values. This review article is in pursuit of giving detailed information on the pharmaceutical basis of their design, classification, advantages, in vitro evaluation parameters. Controlled release (CR) dosage forms have been extensively used to improve therapy with several important drugs. The recent developments of floating drug delivery systems (FDDS) including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance and application of floating systems. Floating dosage form can be prepared as tablets, capsules by adding suitable ingredients as well as by adding gas generating agent. In this review various techniques used in floating dosage forms along with current & recent developments of stomach specific floating drug delivery system for gastro retention are discussed.

Nebivolol Hydrochloride is a third generation beta blocker used for the treatment of hypertention and heart failure. Nebivolol is rapidly absorbed following oral administration, reaching peak plasma concentrations in 0.5 – 4.0 hrs. The present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) for Nebivolol Hydrochloride employing various ratios of hydrophilic and hydrophobic polymers by solvent casting technique. The developed patches were then evaluated for physicochemical characterization, ex-vivo permeation and skin irritation studies. The compatibility of drug with other ingredients was checked by FTIR studies. FTIR results revealed that there was no interaction between dug and other excipients. The transdermal patches obtained were transparent, smooth, uniform and flexible. The results of physicochemical properties were within the pharmacopoeial limits. All the formulations were subjected to ex-vivo skin permeation study by means of Franz’s diffusion cell in order to optimize the suitable formulation. Two formulations with the polymeric blend 3:2 (HPMC E50: ERL 100 and HPMC E15: ERL100 respectively) showed an increase in permeation of drug via skin when compared with the formulations having less proportion of hydrophilic polymer (HPMC), however the formulation with HPMC E50 : ERL 100 showed overall improvement in flux and permeation, hence it was optimized as suitable matrix system. The drug release follows zero order kinetics with diffusion mechanism. The average steady state flux obtained with HPMC E50: ERL 100 (3:2) was 43.3 µg/cm2/hr and the same was increased to 59.2 µg/cm2/hr with the incorporation of 5% v/w of DMSO as permeation enhancer. In conclusion, the present data confirm the feasibility of developing Nebivolol Hydrochloride transdermal system. The release rate of drug through patches increased when the concentration of hydrophilic polymer was increased. 

It is well known that solid oral dosage forms, particularly tablets, are the most acceptable form of delivering medication. However, some new variations are beginning to emerge such as mini-tablets, which offer formulation flexibility. A multifunctional and multiple unit system for oral use are developed by filling versatile mini-tablets in a hard capsule. Multipulsatile DDS, site-specific DDS, zero-order DDS, slow/quick DDS, and quick/ slow DDS are designed in different ways and are investigated. Mini-tablets are small tablets with a diameter typically equal to or less than 3 mm that are typically filled into a capsule, or occasionally, further compressed into larger tablets. It is possible to incorporate many different mini-tablets, each one formulated individually and programmed to release drug at different sites within the gastrointestinal track, into one capsule. These combinations may include immediate release, delayed release, and/or controlled release mini-tablets. It is also possible to incorporate mini-tablets of different drugs to treat concurrent diseases or combinations of drugs to improve overall therapeutic outcome, while delivering distinct release rates of each according to disease requirements. Mini-tablets combine the advantages of multiparticulate dosage forms with the established manufacturing techniques of tableting. Additional benefits of mini-tablets include excellent size uniformity, regular shape and a smooth surface, thereby offering an excellent substrate for coating with modified release polymeric systems. From this, study it can be concluded that, granules-mini-tablets filled in HPMC capsule systems and coated mini-tablet-in-HPMC capsule system sulphate shows both sustained release as well as immediate release may improve the bioavailability and efficacy of any drugs. Keywords: Mini-tablets, immediate-release, delayed-release, controlled-release, multiparticulate dosage forms.

  The objective of the present study was to prepare and evaluate gastroretentive effervescent floating drug delivery system containing Zidovudine as a model drug. Zidovudine is the first approved compound for the treatment of AIDS; however the main limitation to therapeutic effectiveness of zidovudine is its dose-dependent toxicity, short biological half-life and poor bioavailability. Zidovudine gastroretentive effervescent floating tablets were prepared by direct compression method. Sodium bicarbonate and citric acid were incorporated as gas-generating agents. Drug compatibility with excipients was checked by DSC and FTIR studies revealed that, there was no incompatibility of the drug with the excipients used. The results of in-vitro buoyancy time and lag time study, the values of in-vitro buoyancy time ranges from 180 to 870 min where as floating lag time ranges from 2.11 to 51.36 min. The formulations prepared with carbopol have longer floating lag times. The formulation GREFT-6 shows the lag time 2.11 min and buoyancy time 870 min. The release of Zidovudine from all the formulations ranges from 45.05 - 64.96 % drug released at the end of 6 hrs. The formulations GREFT-1 and GREFT-2 shows 90 % of drug release within 10 hrs. The formulations GREFT-3 to GREFT-7 shows drug release ranges from 86.17 - 96.65 % at the end of 12 hrs. The results were revealed that as the concentration of carbopol increases, there is decrease in the drug release and floating time has been increased. The formulation GREFT-6 containing Carbopol 934P 100 mg showed the controlled drug release when compare to other formulations. The stability study conducted as per the ICH guidelines and the formulations were found to be stable. From the above studies, it has been observed that effervescent based floating drug delivery system is a promising approach to achieve controlled release behavior. Key wards: Zidovudine, HPMC K4M, carbopol, floating tablets, effervescent.

  Nimodipine is an antihypertensive, calcium channel blocker, vasodilator agent and used in the treatment of various cardiovascular disorders such as angina pectoris, cardiac arrhythmia and hypertension. Oral bioavailability of Nimodipine is around 13% and having half life 9 hrs. In present research work an attempt has been made to prepare fast dissolving tablets of Nimodipine by direct compression technique with β-cyclodextrin complexes using various superdisintegrants. The powder blends were subjected for pre-compressional parameters. The prepared tablets were evaluated for post-compressional parameters. The prepared tablets were characterized by DSC and FTIR Studies. No chemical interaction between drug and excipients was confirmed by DSC and IR studies. The values of pre-compression parameters evaluated were within prescribed limits and indicated good free flowing property. All the post-compressional parameter are evaluated were prescribed limits and results were within IP acceptable limits. The tablets were evaluated for the in-vitro disintegration time and it was observed that the time for all the formulations varied from 19.24 to 48.29 sec. The promising formulations CCP4, CCC4 and CSS1 shows the 90 % of drug released within 5-8 min. Among all the formulation CCP4 (15 % crospovidone) were found to be best and showed a disintegration time of 19.24 sec, 50 % of drug released in 0.96 min, and 90 %  of drug released in 4.78 min. The stability study was conducted as per the ICH guidelines and the formulations were found to be stable, with insignificant changes in hardness, drug content and disintegration time. These results revealed that fast dissolving tablets of the poorly soluble drug, Nimodipine, showing enhanced dissolution and, hence, better patient compliance. Key words: Fast dissolving tablets, Nimodipine, sodium starch glycolate, croscarmellose sodium, crospovidone,  β-cyclodextrin.