Fast-release Tablets Research Articles

A Novel Lactose/MCC/L-HPC Triple-Based Co-Processed Excipients with Improved Tableting Performance Designed for Metoclopramide Orally Disintegrating Tablets.

New co-processed excipients comprising lactose (filler and sweetener), microcrystalline cellulose (MCC, filler), and low-substituted hydroxypropyl cellulose (L-HPC, disintegrant and binder) were developed via solvent evaporation for the preparation of metoclopramide orally disintegrating tablets (MCP ODTs). Single-factor and Box-Behnken experimental designs were employed to optimize the formulation. The optimized formulation ratios were water: MCC: lactose (g/g) = 17.26:2.79:4.54:1. The results demonstrated that particles formed by solvent evaporation had superior flowability and compressibility compared to the physical mixture. Tablets compressed with these co-processed excipients exhibited a significantly reduced disintegration time of less than 25 s and achieved complete dissolution within 5 min. Pharmacokinetic studies revealed that MCP ODTs significantly improved Cmax, which was 1.60-fold higher compared to conventional tablets. In summary, the lactose/L-HPC/MCC triple-based co-processed excipients developed in this study are promising and could be successfully utilized in orally disintegrating and fast-release tablets.

D-optimal mixture design inspired modified release tablet formulation of lamotrigine for the treatment of seizures: An in-depth characterization

Lamotrigine (LTG) an anticonvulsant drug with a dissociation constant (pKa: 5.7), suffers from enhanced blood plasma spike after each dose, when administered as fast release tablet. Being BCS class-II candidate and pH dependent solubility, development of release-controlled tablets of LTG is a major challenge. This investigation aims at designing the release-controlled tablet (RCT) formulation of LTG using a solid dispersion (SD) technique via addressing its solubility and release problems. RCT of LTG was fabricated using SD blend of Eudragit RL and Eudragit RS and PVP K-30 with different polymer blend ratio (1:5 and 1:7). The optimization of RCT of LTG was performed using D-optimal mixture design with three independent variables, three response variables, and one constraint. The dissolution rate was determined and data were then fitted to different mathematical models. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies and tableting parameters were analyzed. In vitro studies of predicted optimized batches (POBs) have shown that drug release over a period of 12hours was 88.05±3.4% in media I, 86.10±3.7% in media II and 85.84±4.2% in media III. An in vitro kinetic model equating R2-value for all the tested models indicated that the first order and Higuchi release kinetics model were the most appropriate. Based on the optimized formulation consisting of SD of LTG with Eudragit RL, Eudragit RS and PVP K-30, the release rate was consistently similar throughout the GI tract, regardless of the pH of the environment.

Comparison of gastrointestinal adverse events between fast release tablets and regular acetylsalicylic acid (aspirin) galenics after short-term use: a meta-analysis of randomized clinical trials.

This study aimed at determining whether there is a difference in the safety profile between fast release (FR) aspirin tablets and regular galenic formulations of aspirin. This study was based on a clinical study database pool (Bayer HealthCare) including 84clinical studies and 16,095human subjects. The meta-analysis included 72studies applying a single dose of aspirin of at most 1000mg and was, therefore, based on individual data from 9288subjects. Of these, 6029subjects took aspirin and 3259subjects took placebo. Endpoints were adverse events (AEs) of any kind and, especially of gastrointestinal (GI) nature. Event incidence and odds ratios (OR) based on Mantel-Haenszel risk estimates were calcuated. Subjects on aspirin FR had a significantly decreased OR of 0.65 [0.48, 0.90] [95% confidence interval] for all AEs and of 0.39 [0.20, 0.79] for drug-related all AEs versus placebo. The risk of all GI AEs tended to be reduced for subjects on aspirin FR (0.65 [0.41; 1.03]), but not for drug-related GI AEs. Subject on aspirin mono and aspirin mono (plain only, w/o FR) showed an increased risk of drug-related all AEs compared to placebo (1.34 [1.11; 1.62] and 1.43 [1.13; 1.80]). However, subjects on aspirin FR and those on regular aspirin had almost the same risk of all determined AEs. In conclusion, aspirin FR tablets showed a comparable GI tolerability to regular galenic formulations of aspirin after short-term treatment. Major GI complication did not occur after intake of any galenic formulation of aspirin.

Development of fast release tablet of talinolol using fourth generation carrier of solid dispersion technique

Talinolol is a beta1-selective adreno receptor antagonist well known for its Cardio protective and antihypertensive activity. Talinolol is a beta blocker. In biopharmaceutical classification system the drugs which come under class II are characterized by more membrane permeability, less dissolution rate. Talinolol is a poor aqueous solubility drug leads to poor bioavailability. So, the aimed of this study was to develop immediate release tablet of talinolol by solid dispersions technique using poloxamer 407 as a carrier. Poloxamer 407 is a hydrophilic synthetic block copolymer widely used as a solubility enhancer. Basically there are three methods used for solid dispersion. Melting or fusion method solvent evaporation method. Melting solvent method. Solvent Evaporation Method In this method a suitable solvent is selected which can capable of solubilizing both drug and hydrophilic carrier. The solvent evaporation technique is one of the most commonly used methods to prepare polymeric nanoparticles, more specifically drug-loaded polymeric systems, for pharmaceutical formulations. The prepared solid dispersions were evaluated for production yield percent, drug content, solubility, FTIR, and DSC study analysis. The prepared formulation of Talinolol with P407 in the ratio of 1:5 gave highest dissolution rate of 75.28% at 30min.So it can be concluded that the combination of solid dispersion technology as well as using superdisintergrants an encouraging and effective technique to prepare efficient fast dissolving tablets of Talinolol.The outcome of this investigation presents poloxamer 407 solid dispersion mediated fast dissolving tablets successfully resolve problem of slow rate of dissolution of talinolol.

Exploration of melt granulation technique for the development of entecavir monohydrate tablets using 32 factorial designs

This research work aims to fabricate fast-release tablets of entecavir monohydrate using a novel melt granulation technique and optimize the proportion of xylitol and mannitol using a 32 factorial design. entecavir monohydrate, a medication used for treating hepatitis B virus (HBV) infection, was used as a model drug. The fast-release tablets were designed to avoid fluctuations in plasma drug concentration and increase the bioavailability of entecavir monohydrate. The FTIR spectra of pure entecavir monohydrate were compared against polymers which had no interaction. The pre-compression and post-compression parameters were found to be within the desired range. The results of the drug release studies indicate that the formulations were able to release the drug within the desired range of 60-80% within 10 minutes. The study concludes that the melt granulation technique can be used to develop fast-release tablets of entecavir monohydrate with good compressibility, flow characteristics, and mechanical strength.

Chitosan-Based Nanoparticles for Targeted Nasal Galantamine Delivery as a Promising Tool in Alzheimer's Disease Therapy.

Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer's dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan-alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size of the GH-loaded chitosan NPs was about 240 nm, while the sodium alginate coated chitosan particles loaded with GH were expectedly bigger, with a mean particle size of ~286 nm. GH release profiles in PBS at 37 °C were obtained for both types of NPs, and it was found that the GH-loaded chitosan NPs allowed the prolonged release of the incorporated drug for a period of 8 h, while the complex GH-loaded chitosan/alginate NPs released the incorporated GH faster. The stability of the prepared GH-loaded NPs was also demonstrated after 1 year of storage at 5 °C ± 3 °C.

A Review on Formulation and Evaluation Approaches for Fast Release Tablet

A Review on Formulation and Evaluation Approaches for Fast Release Tablet

An ultrasonographic assisted investigation for the enhancement of duodenal/cecal motility of mosapride through a surfactant-based triple solid dispersion: In-vitro, in-vivo assessment of tablet formulation

Gastrointestinal (GI) disorders affect millions of people and are considered a major cause of global morbidity. Mosapride citrate (MOS) is a prokinetic agent with antiemetic effect. The drug suffers from poor bioavailability that is induced by its low solubility. The present study aimed to enhance the in-vivo performance of the drug through formulation of fast release tablets. Both binary (SD) and triple solid dispersion (TSD) were prepared with Soluplus® (SOL) and α-Tocopherol polyethylene glycol succinate (TPGs) using solvent evaporation. Optimal systems were chosen according to the best dissolution rate and were compressed into tablets using either, AcDiSol, Crospovidone, or chitosan as superdisintegrants. Results declared that MOS-TSD acquired the highest dissolution rate in terms of t1/2 = 1.5 min. DSC and XRPD illustrated a partial amorphization of mosapride. FTIR revealed a possible H bond interaction between drug and carriers. Drug release from MOS-TSD tablets containing Crospovidone showed 60.7% flush release with a t1/2 = 1.4 min. An ultrasonographic study performed on rabbits revealed that MOS-TSD tablet with optimum carrier combination showed 2.46 -fold increase in duodenal and cecal motility compared to pure MOS and 2.5-fold increase compared to the oral marketed product. Therefore, the formulation of fast release tablet with surfactant based triple solid dispersion offered a great success in improving the therapeutic efficacy of mosapride.

10122 Development of an In Vitro in Vivo Correlation of Itraconazole Spray-Dried Dispersion Tablets

ABSTRACT IMPACT: As the number of poorly water-soluble drugs in development increases, our research will expand on the science behind improving drug solubility and absorption and ensuring that promising poorly-water solubility drugs do not fail drug development. OBJECTIVES/GOALS: Spray-dried dispersion (SDD) tablet formulation is an approach to increase oral drug solubility and absorption. Methods to predict SDD performance in humans are poorly developed. We aim to develop an in vivo in vitro correlation (IVIVC) between in vitro dissolution and in vivo absorption of itraconazole SDD tablets. METHODS/STUDY POPULATION: This research project involves tablet manufacturing, in vitro dissolution experiments, and a clinical study. We manufactured fast-, medium-, and slow-release SDD tablets containing amorphous solid dispersion of itraconazole (100 mg) and different grades of the polymer hypromellose acetate succinate (HPMC-AS). Tablets differed in slug pressure, tablet compression force, and formulation composition. Dissolution studies were performed using the United States Pharmacopeia (USP) type II apparatus. The clinical study is an ongoing randomized, cross-over, open-label, fasted, single-dose trial in healthy participants (n=12). An IVIVC will be created by comparing the rank order of drug in vitro dissolution with in vivo absorption. RESULTS/ANTICIPATED RESULTS: Tablet manufacturing was successful, and the tablets displayed the same dissolution rate ranking order as anticipated. Fast-release tablets showed the highest percentage of drug dissolved by 10 min (74%) compared to medium- (62%) and slow-release (1.2%) tablets. Percentage drug dissolved differs by at least 10% at all time points among the different release-rate tablets. The clinical study is currently ongoing, and we expect that the pharmacokinetic (PK) profiles differ among the different tablets. We predict that the rank order of tablet absorption in humans will agree with the order of drug dissolved observed in the dissolution experiments. DISCUSSION/SIGNIFICANCE OF FINDINGS: Spray-dried dispersions are a formulation method to try to improve drug solubility and oral drug absorption. This research will elucidate manufacturing parameters that can impact tablet performance and expand on the ability of in vitro dissolution to predict human PK and streamline drug development of poorly soluble drug candidates.

Solidification of SMEDDS by fluid bed granulation and manufacturing of fast drug release tablets

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is a rising experimental field with important potential for pharmaceutical industry, however fluid-bed granulation with SMEDDS is yet an unexplored solidification technique. The aim of the study was to solidify carvedilol-loaded SMEDDS utilizing fluid bed granulation process and to investigate how the formulation variables (type of solid carrier, optimization of granulation dispersion) and fluid-bed granulation process variables can be optimized in order to achieve suitable agglomeration process, high drug loading and appropriate product characteristics. Obtained granulates exhibited complete drug release, comparable to liquid SMEDDS and superior to crystalline carvedilol, nevertheless compromise between large SMEDDS loading and appropriate flow properties of the granules has to be made. Representative granulates with highest drug loading were further compressed into tablets. It was shown that the optimal excipient selection of compression mixture and compression force can lead to fast carvedilol release even from the tablets. Selfmicroemulsifying properties were not impaired neither after the solidification process and nor after the compression of solid SMEDDS into tablets. This suggests that fluid-bed granulation with SMEDDS offers a perspective alternative for solidification of the SMEDDS, enabling preservation of self-microemulsifying properties, acceptable drug loading and complete drug release.

Thermoresponsive poly(N-isopropylacrylamide) copolymer networks for galantamine hydrobromide delivery

Natural alkaloid galantamine is widely used for the treatment of Alzheimer’s disease and various other memory impairments. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solution. However, oral delivery of GH can cause side effects, such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery is one possible way to avoid such unwanted effects and is also patient friendly, especially for unconscious patients, patients with swallowing difficulties, and patients with mental disturbances. In this work, thermoresponsive copolymer networks based on poly(N-isopropylacrylamide) were studied as new platforms for potential transdermal GH delivery. Series of networks of varied structure and composition were synthesized and investigated by applying swelling kinetics and different spectroscopic and thermal methods. The network films were drug loaded in GH aqueous solution and main characteristics of the obtained GH delivery systems were evaluated. The GH release kinetic profiles in BS at 37 °C were established and discussed.

A fast release tablet containing herbal extracts (Ginger, Cinnamon, Turmeric, Long pepper and Punarnava)

A fast release tablet containing herbal extracts (Ginger, Cinnamon, Turmeric, Long pepper and Punarnava)

IVABRADINE HYDROCHLORIDE DIRECTLY COMPRESSED TABLETS USING NANO-CELLULOSE EXTRACTED FROM ARACHIS HYPOGAEA SHELLS

Objective: The main objective of this work was the extraction of nanocellulose from Arachis hypogaea shells, characterization of nanocellulose, development, and in vitro evaluation of directly compressed tablets of ivabradine hydrochloride (IVH) using nanocellulose.
 Methods: IVH and colloidal silicon dioxide are gift samples from Mylan Laboratory, Hyderabad, and Karnataka Antibiotics and Pharmaceuticals Ltd., Bengaluru, respectively. Nanocellulose was extracted from A. hypogaea shells by alkaline treatment followed by acid hydrolysis and it was characterized by particle size analysis by zeta sizer, melting point determination, differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis. Compatibility between IVH and nanocellulose was confirmed by FTIR and DSC analysis. Then, fast-release tablets of containing 5 mg of IVH were prepared by direct compression using various compositions containing nanocellulose, starch, and colloidal silicon dioxide and evaluated.
 Results: Nanocellulose in the size of 273.4 nm was extracted from A. hypogaea shells to possess its ideal characteristics. IVH and nanocellulose were compatible according to FTIR and DSC analysis. Fast-release tablets of IVH were prepared as directly compressed tablets by direct compression. Tablets made with 5 mg of IVH and nanocellulose, starch, and colloidal silicon dioxide evidenced fast release of 96.37% in 5 min.
 Conclusion: Nanocellulose from A. hypogaea shells can be produced successfully by alkali treatment followed by acid hydrolysis, ball milling, and lyophilization. This nanocellulose can be exploited successfully for the design of fast-release tablets of IVH.

Preparation and assessment of poly(methacrylic acid-coethylene glycol dimethacrylate) as a novel disintegrant

Purpose: To prepare and evaluate poly(methacrylic acid (MAA)-co-ethylene glycol dimethacrylate (EGD)) as a tablet disintegrant. Methods: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms at cross-linker (EGD) levels of 0.25 -16 % were synthesized and subjected to Fourier transform infrared spectroscopy. Swelling capacity, disintegration efficiency and cytotoxicity to Caco-2 cells were determined using standard procedures. Results: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms were successfully prepared. In contact with water, the polymers in Na form swelled more than those in H form. The swelling capacities of polymers in H and Na forms decreased with increasing amounts of cross-linker. Incorporation of the polymers accelerated the disintegration of microcrystalline cellulose tablets (placebo), and the disintegration efficiency depended on the salt form and amount of cross-linker. The Na salt form of the polymer crosslinked at 16 % EGD was the best candidate disintegrant. When used at 2.5 and 10 %, the selected polymer effectively promoted the disintegration and drug release of propranolol hydrochloride tablets. Moreover, cytotoxicity tests showed that it was non-toxic to Caco-2 cells. Conclusion: The developed poly(MAA-co-EGD) possesses good disintegration and dissolution functionalities. Thus, it may be adopted as a new super-disintegrant for fast-release tablets. Keywords: Tablet disintegrant, Methacrylic acid, Ethylene glycol dimethacrylate, Propranolol hydrochloride

FORMULATION, EVALUATION AND DEVELOPMENT OF FAST RELEASE TABLETS OF ROSUVASTATIN CALCIUM USING SUBLIMATION METHOD

FORMULATION, EVALUATION AND DEVELOPMENT OF FAST RELEASE TABLETS OF ROSUVASTATIN CALCIUM USING SUBLIMATION METHOD

Effect of Different Meltable Binders on the Disintegration and Dissolution Behavior of Zolmitriptan Oromucosal Fast Melt Tablets

Objective: Fast melt tablets and sublingual route have been widely used for providing quick onset of action with the avoidance of first pass metabolism. The objective of this work was to compare the effect of different meltable binders namely; polyethylene glycol (PEG) 4000, pluronic F127 and pluronic F68 on the performance of fast release tablets of the model drug zolmitriptan prepared using the melt granulation technique regarding disintegration time (DT) and dissolution rate (DR) as criteria for rapid absorption and hence quick onset of action. Zolmitriptan is a potent antimigraine drug. Current oral zolmitriptan tablets suffer from slow onset of action, poor bioavailability and large inter-subject variability. Methods: 33 factorial design was adopted. The effect of binder type, binder concentration and croscarmellose sodium (disintegrant) concentration were studied on DT and DR. Results: The three factors were found to significantly affect the DR and the inverse square root of DT and significant interactions were elucidated. Conclusion: Although satisfactory results were obtained regarding DR, modifications using different excipients and or preparation methods should be considered to comply with pharmacopoeia requirement for DT.

EFFECT OF NATURAL AND SYNTHETIC POLYMERS ON THE PROPERTIES OF CANDESARTAN CILEXETIL MATRIX TABLET PREPARED BY DRY GRANULATION

ABSTRACTObjective: The objective of this study is to develop a controlled release matrix tablet of candesartan cilexetil to reduce the frequency of administration,enhance bioavailability and improve patient compliance; a once daily sustained release formulation of candesartan cilexetil is desirable.Methods: The prepared tablets from F1 to F24 were evaluated with different evaluation parameters like weight variation, drug content, friability,hardness, thickness and swelling ability. In vitro release for all formulas were studied depends on the type and amount of each polymer, i.e. (16 mg,32 mg and 48 mg) respectively beside to the combination effect of polymers on the release of the drug from the tablet.Results: In vitro release showed that formula 13 had the faster release (100% after 4 h) which contained acacia (1:1) and the lowest sustain releasewas showed for F7 (73% after 8 h) which contained HPMC K100M (1:1). Formula 1 was an 89 % release after 8 h which contain eudragit RS100; F4was a 100 % release after 5 h which contain Na CMC, F10 was a 100% after 8 h which contain xanthan gum and F16 was a 100 % release after 5 hwhich contain tragacanth polymer. Formula 9 had a lower release than F7 and F8 respectively. Formula 7 can be used for sustain oral drug delivery ofcandesartan cilexetil while Formula 13 can be used in contrary as fast release tablets for faster response.Conclusion: Controlled drug delivery system is promising for less dosing and higher patient compliance.Keywords: Angiotensin II receptor antagonist, Hypertension, Matrix system, Control release.

Development of Fast Dissolving Tablets of Nisoldipine by Solid Dispersion Technology using Poloxamer 407 and Poloxamer 188

Objective: The aim of the present study is to design oral fast-release tablets of nisoldipine and to optimize the drug dissolution profile by modifying the carrier concentration. Poloxamer 407 and Poloxamer 188 were selected as carriers for preparing the solid dispersion (SD) by solvent evaporation method with different drug polymer ratios. Methods: The prepared solid dispersions were analyzed for physical state, drug:carrier interactions by Xray diffraction, infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. Results: The dissolution studies revealed that all solid dispersions showed increased dissolution rate whencompared to pure nisoldipine. Among the two polymers used, poloxamer 407(P 407) was found to be better than poloxamer 188(P 188) in the enhancement of dissolution efficiency. The tablets were formulated using solid dispersion of nisoldipine containing poloxamer 407 as carrier. Conclusion: The results exhibited that poloxamer 407 SD based tablets gave a significantly higher release of nisoldipine when compared with control tablets. Infrared spectral studies showed that there was no interaction between thenisoldipine and its formulation with different carriers used in the preparation of solid dispersions. X-ray diffraction studies revealed that the degree of crystallinity of nisoldipine decreased when the concentration of carriers increased, which showed that the drug is in amorphous nature. Key words: Fast dissolving tablets, Poloxamer 407, Poloxamer 188, Solid dispersion, Superdisintergrants.

Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters.

Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

Characterization and evaluation of a modified PVPA barrier in comparison to Caco-2 cell monolayers for combined dissolution and permeation testing

Aim of this study was to implement a modified phospholipid vesicle-based permeation assay (PVPA) barrier as alternative to Caco-2 cell monolayers in a combined dissolution and permeation system for testing of solid dosage forms. Commercially available Transwell® inserts were coated with egg phospholipids (Lipoid E 80) and characterized by confocal Raman microscopy. The modified PVPA barrier was then evaluated in permeation studies with solutions of different drugs as well as in combined dissolution and permeation studies utilizing an immediate and an extended release tablet formulation.Raman cross section images demonstrated complete filling of the membrane pores with lipids and the formation of a continuous lipid layer of increasing thickness on top of the membrane during the stepwise coating procedure. Furthermore, it could be shown that this lipid coating remains intact for at least 18h under dynamic flow conditions, significantly exceeding the viability of Caco-2 cell monolayers.Permeability data for both drug solutions as well as for a fast and slow release tablet formulation were in excellent correlation with those data obtained for Caco-2 cell monolayers. Especially under the dynamic flow conditions prevailing in such a setup, the modified PVPA barrier is more robust and easier to handle than epithelial cell monolayers and can be prepared rather easily at a fraction of costs and time. The modified PVPA barrier may therefore represent a valuable alternative to Caco-2 cell monolayers in such context.