Extended-release Tablets Research Articles

Gastro retentive floating drug delivery system of model drug using central composite design

The work plans to build up a Gastro retentive floating drug delivery system of Model drug using central composite design. The model drug is a drug which is used in the treatment of antiulcer. Extended-release tablets of model drug provide constant plasma concentration with a less frequent administration and also reduce the side effects to some extent. This could extend its safe administration and improve patient compliance. The present study aims to develop floating tablets of model drug using HPMC K4M, Carbopol 934 and an effervescent agent which can float on gastrointestinal fluid for sustained release and evaluate the model drug tablets in-vitro for their TFT, FLT, and drug release pattern. Gastro retentive drug delivery system (GRDDS) refers to systems in which the drug retained in the stomach for a prolonged period that improves the bioavailability of drug substances. Any delivery system aims to deliver a therapeutic amount of drug to the specific site in the body to obtain rapid and then maintain a requisite amount of drug. The formulated tablets evaluated for both pre-compression and post compression parameters including weight variation, hardness, friability, in vitro drug release and different pharmacokinetic plots. Final formulation was agreeable when assessed for all assessment parameters.

Incidence of Delirium With Different Oral Opioids in Previously Opioid-Naive Patients.

Background: Opioids are known to induce delirium, but few studies have closely investigated differences in incidence of delirium among different opioids. Objectives: To determine whether there is a clinically significant difference in the incidence of delirium between oral opioids in previously opioid-naive patients. Methods: Subjects were 259 opioid-naive in-patients with cancer who were started on morphine sulfate, oxycodone hydrochloride, or tapentadol hydrochloride extended-release tablets at our hospital between August 1, 2014, and September 30, 2018. The incidence of delirium during the first week of treatment was compared between the drugs. Results: The incidence of delirium was 4.8% (n = 83) for morphine sulfate, 6.9% (n = 131) for oxycodone hydrochloride, and 6.7% (n = 45) for tapentadol hydrochloride. The incidence did not significantly differ between oxycodone hydrochloride (OR = .69, 95% CI = .20–2.30, P [Fisher’s exact test] = .77) or tapentadol hydrochloride (OR = .71, 95% CI = .15–3.32, P [Fisher’s exact test] = .70) and morphine sulfate (reference group). Moreover, the incidence did not significantly differ between tapentadol hydrochloride (OR = 1.03, 95% CI = .27–3.00, P [Fisher’s exact test] = 1.00) and oxycodone hydrochloride (reference group). Conclusion: The incidence of delirium in previously opioid-naive patients did not differ significantly among morphine sulfate, oxycodone hydrochloride, and tapentadol hydrochloride extended-release tablets, suggesting similar risk of delirium in opioid-naive patients among these oral opioids.

Time within therapeutic range: A comparison of three tacrolimus formulations in renal transplant recipients

Background: Currently there are three available formulations of tacrolimus in the United States; these include immediate-release capsules (TAC-IR), extended-release capsules (TAC-XL), and extended-release tablets (TAC-XR). Previous studies have demonstrated non-inferiority between the three formulations in terms of efficacy. The purpose of this study was to compare three formulations of tacrolimus (TAC) and assess differences in time within the therapeutic range (TTR) and variability in levels. Results: Renal transplant recipients from January 2013 to October 2017 were retrospectively identified for analysis. Deviation from standard TAC protocol or formulation changes excluded patients. The primary outcome compared percent TTR (TTR %) among 3 TAC formulations over the first 90 days post-transplant. TTR was calculated using the Rosendaal method. Secondary outcomes included differences in TAC levels, TAC dose, eGFR, rejection, patient and graft survival between the TAC formulations. TAC-XR demonstrated a significantly higher TTR % compared to TAC-IR and TAC-XL (62.8% vs. 53.3% vs. 60.9%, p = 0.048). In post-hoc analysis, TAC-XR had a higher TTR % compared to TAC-IR (p = 0.065), which approached statistical significance. Average TAC levels, weight-normalized TAC doses, median dose-normalized TAC levels, rejection rates, eGFR, and graft or patient survival were similar among groups. Conclusion: In the early transplant period, TTR was significantly different among the groups. TAC-XR demonstrated numerically superior time within the therapeutic range. Patient-specific factors such as race, obesity, genetic polymorphisms may impact this variability and clinical outcomes. Further analysis is necessary to understand the effect of each patient-specific factor on TAC exposure.

Effect of coating material on dissolution profile of BCS class 1 anti-epileptic extended-release tablets

The coating is one of the crucial phases in the production of the tablet dosage form with extended-release profiles. Tablet coating has numerous benefits, including disguising the medicine's odor, taste, physicochemical protection, and safeguarding the drug from the stomach environment. The aim to conduct this study was to determine the effect of varying concentrations of coating solutions on dissolution profiles. Extended-release tablet dosage form of antiepileptic drug as a prototype was developed to ensure minimize fluctuation in drug plasma levels. Tablets were prepared using two grades of HPMC methocel K100 and methocel K15 H, along with anhydrous lactose and microcrystalline cellulose followed by film coating using different concentrations of opadry white via spraying method, and results were compared with the marketed formulation.

Investigating the Influence of Cellulose and Acrylic Based Polymers on Guanfacine Loaded Extended-Release Tablets

Investigating the Influence of Cellulose and Acrylic Based Polymers on Guanfacine Loaded Extended-Release Tablets

Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients with Multiple Sclerosis: An Open-Label Extension Study

Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients with Multiple Sclerosis: An Open-Label Extension Study

Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients with Multiple Sclerosis: A Randomized, Placebo-Controlled Clinical Trial

Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients with Multiple Sclerosis: A Randomized, Placebo-Controlled Clinical Trial

Development and Evaluation of Extended Release Tacrolimus Tablets by Melt Granulation in Combination with Magnesium Alumino Metasilicate

To increase the effectiveness of tacrolimus, the present study sought to develop extended-release tablets. It is used to treat mild to severe atopic dermatitis as well as to prevent organ rejection after organ transplantation. Tacrolimus, on the other hand, has a poor bioavailability and a short half-life. The current research aims to create extended-release tacrolimus tablets by melting and granulating utilizing lipid and adsorbent materials to ensure excellent flow and a hypromellose matrix system to regulate release for 12 hr. Tacrolimus granules were prepared by melting with glyceryl behenate in rapid mixer granulator in the presence of polyethylene glycol followed by magnesium alumino metasilicate for adsorption purposes. Adsorbed granules were milled, sifted, and mixed with extra granular material such as hypromellose, lactose monohydrate and magnesium stearate. Granules were compressed to tablets using oval-shaped plain tooling. In vitro dissolution profile of solid dispersion and extended release tablets were investigated. Release profile of tablets and solid dispersion were improved by melt granulation due to the polymorphic form conversion of drug substance from crystalline to amorphous.Release kinetics of tacrolimus extended release tablets were fitted with zero order release with R2 value of 0.964, which designate constant release for 12 hr. Therefore, the present findings from the study revealed that the formulation was successfully prepared and showed extended release pattern over 12 hr.

Progress and Characterization of Pramipexole Extended-Release Tablets

Pramipexole dihydrochloride monohydrate is an antiparkinson’s agent which is known as dopamine D2 receptor agonist. It is structurally different from the ergot-derived drugs, e.g. bromocriptine or pergolide. Pramipexole is designated chemically as (S)-2-Amino-4, 5, 6, and 7- tetrahydro-6-(propylamino) benzothiazole and has the molecularformula C10H17N3S. It comes under class I of Biopharmaceutical Classification System. The purpose of this study was to develop and evaluate pramipexole dihydrochloride monohydrate extended release tablets by wet granulation method using different proportions of polymers and binder. Pre-formulation studies were done initially and the results were found to be within the limits. All the mentioned batches were prepared and granules were evaluated for pre-compression parameters such as loss on drying, bulk density, tapped density and compressibility index. Tablets were evaluated for weight variation,thickness, hardness, friability; disintegration time and assay were found to be within the limits. In vitro dissolutions were performed with 0.05M 6.8 PH phosphate buffer and effectof various polymerswere explored. Final selection of formulation was based on dissolution profile,from dissolution studies formulation 9 showed 80% drug release within 20 hours, so it will be compared with innovator. Similarity and difference factors which revealed that formulation (F 9) containing HPMC K 200, Eudragit L100 and binderare most successful as it exhibited in vitro drug release that matched with innovator product.In vitro drug release profilereveals that with increased concentration of Eudragit L 100. Accelerated stability studies were performed for the optimized batch which indicatedthat there were no changesin drug contentand in vitro dissolution.

Formulation and evaluation of dexlansoprazole extended-release tablet

Dexlansoprazole (DSP) is a proton pump inhibitor, it used to treat GERD and ulcer colitis. DSP works by decreasing the volume of acid in the stomach. DSP is an acid-labile medication that may be destroyed in the stomach's acidic pH. A coating technique was used to postpone drug release in the stomach, which can extend pharmacological activity. Shellac can be used to develop the sustain release tablet of dexlansoprazole as retardation of the drug (dexlansoprazole) was observed in the acidic pH of the stomach, and hence a sustain coated dexlansoprazole tablet was prepared and evaluated. The coating's primary function is to allow for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits faster degradation in the acidic pH of the stomach, therefore increasing pharmacological action. DSP coating with different polymers inhibits fast degradation in the stomach's acidic pH, enhancing pharmacological action. The major function of the coating is to enable for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits fast breakdown in the stomach's acidic pH, enhancing pharmacological action.

Formulation and evaluation of dexlansoprazole extended-release tablet

Formulation and evaluation of dexlansoprazole extended-release tablet

Formulation design and Evaluation of Extended-Release Tablets of Oxybutynin for Effective Management of Overactive Bladder Syndrome

Overactive bladder syndrome (OAB) is a chronic condition with a composite of symptoms and has a significant negative impact on the physiological and psychological well-being of the patients. The present study is aimed at developing extended-release formulations of oxybutynin that is effective in reducing the side effects associated with the drug by maintaining a steady state concentration with minimal fluctuations in plasma drug concentration and thereby achieves improved patient compliance. The extended-release drug delivery of tablets can be achieved by preparing the matrix tablet of oxybutynin chloride with klucel HF in core tablet by wet granulation technique and functional coating with a combination of aquacoat ECD-30 and hypromellose E5 followed by film coating with opadry. For confirmation of compatibility, the pure drug and its physical mixtures were subjected to FTIR studies. All the formulations have shown acceptable limits in all precompression and post compression parameters. The in vitro release studies in 0.1N HCl and 6.8 phosphate buffer revealed that the optimized formulation F10 extend the release of the drug to 91% at 24 hours and the release profile was similar to the innovator’s product as revealed by the similarity factor study. The release kinetics study revealed that the release of the drug followed diffusion mechanism. Stability studies of the selected formulation tablets were carried out at 25°C ±2°C/60% RH±5% and 40°C ±2°C /75%±5% RH for different time period and all the parameter was within the limits after storage period. Thus the extended release matrix tablets of oxybutynin chloride developed in this study have immense potential to develop into a marketed product following the testing in animals and human volunteers.

ROSUVASTATIN CALCIUM NANOSPONGES IN THE FORMULATION OF EXTENDED RELEASE TABLETS

Cyclodextrin has been recognized as a linker molecule that can link with the various drug substances to produce a nano-porous structure called nanosponges (NS) and increase the dissolution rate of poorly soluble drug substances. This work aimed to load rosuvastatin calcium (RSC) with solubility enhancer’s β-cyclodextrin (β-CD) or polyvinyl alcohol (PVA). β-CD based RSC-NS were fabricated by the emulsion solvent diffusion technique; with solubilizer dichloromethane and different ratios of ethyl cellulose as a co-polymer. Characterization of the prepared nanosponges was done by various testing procedures that confirm its nanosize and particle size and drug release. RSC loading in NS was assessed by DSC, FTIR and SEM. Among all the formulations F5 has 78.23 % entrapment efficiency. 2-3 folds of increased solubility were obtained with RSC-NS. F1-F6 formulations released 76.35 % - 98.69 % of the drug at the end of 30 min. In the preparation of extended-release tablets, NS prepared from F5 formulation was used and the best tablet formulation was selected based on various evaluation tests. All the formulations except S3, S8 followed first-order release kinetics. S1 & S2 drug release mechanism is Higuchi while other formulations are Korsemeyer-Peppas, so the release mechanism for most of the formulations is erosion than diffusion.

Formulation and Evaluation of Cefaclor Extended-Release Tablet

Over past 30 years as the expanse and complication involved in marketing new drug entities have increased, with concomitant recognition of the therapeutic advantages of controlled drug delivery, greater attention has been focused on development of extended or controlled release drug delivery systems.
 In the present research work an attempt has been made to optimize, formulate and characterize extended-release tablet of Cefaclor. The preformulation studies were performed for the drug (e.g., physico-chemical properties, melting point, solubility etc.). The drug had shown the results under standard specifications. UV spectroscopic analytical method was also performed for quantitative determinations by plotting standard curve. Before this the pure drug was also scanned for the ƛ max value at different concentrations.
 The pre-compressions parameters and the post compression parameters for the nine formulated tablets were performed. The drug release study of the selected formulations EF3, EF6 and EF9 was performed as those formulations has shown the results within pharmacopoeia limits. The Formulation EF9 was then taken for release kinetic study as it has shown best results among the other three formulations. So, it confirms the drug release by Higuchi diffusion mechanism. From the results, conclusion can be drawn that the formulation consisting 10-12% concentration of hydroxypropyl methyl cellulose K4-M with 1% microcrystalline cellulose and 25% of lactose are considered as ideal for the optimized extended-release tablet formulation for Cefaclor.
 Keywords: Extended release, Cefaclor, Higuchi diffusion mechanism, PBP, bacterial cell wall synthesis.

3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder.

To develop and validate a population pharmacokinetic (PPK) model of valproic acid (VPA) in adult Chinese patients with bipolar disorder, and provide guidance for individualized therapy in this population. A total of 1104 serum concentrations from 272 patients were collected in this study. The data analysis was performed using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, biological characteristics, and concomitant medications. Bootstrap validation (1000 runs), normalized prediction distribution error (NPDE), and external validation of 50 patients were employed to evaluate the final model. A one-compartment model with first-order absorption and elimination was developed for VPA extended-release tablets. VPA clearance was significantly influenced by three variables: sex (12% higher in male patients), daily dose (increasing with the 0.13 exponent), and body weight (increasing with the 0.56 exponent). Typical values for the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) for a female patient weighing 70kg administered VPA 1000mg/day were 0.18h-1, 0.46 L/h, and 12.84 L, respectively. The results of model evaluation indicated a good stable and precise performance of the final model. A qualified PPK model of VPA was developed in Chinese patients with bipolar disorder. This model could be used as a suitable tool for the personalization of VPA dosing for bipolar patients.

Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension

The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 µg·h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.

An In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction

The release and dissolution of an active pharmaceutical ingredient (API) from the solid oral formulation into the gastrointestinal (GI) tract is critical for the drug's absorption into systemic circulation. Extended-release (ER) solid oral dosage forms are normally subjected to physical shear and grinding forces as well as pressure exerted by peristaltic movements when passing through the GI tract. The complex physical contraction and sample friction exerted by the GI tract are not simulated well by compendial dissolution methods. These limitations render traditional in vitro dissolution testing unable to discriminate and predict a product's in vivo performance. The objective of this study was to develop a dissolution method that better simulates the GI environment that products are subject to when taken by patients. A newly designed Mechanical Apparatus under GI Conditions (MAGIC) was assembled with a dissolution platform and mechanical capabilities to allow in vitro dissolution testing under sample contractions and friction. The dissolution platform, with medium flow-through configuration, was manufactured by 3D printing. A 60 mg polymer matrix-based ER nifedipine product was tested. To simulate GI physiological conditions during the dissolution testing, the flow rate of the medium, and a combination of mechanical compression with rotation induced sample friction at various rotation frequencies were explored. The polymer matrix-based nifedipine ER formulation used here failed its controlled release functionality in the simulated GI environment under mechanical compression and sample friction. The results showed that the MAGIC system, with flow-through configuration under compression and sample friction, has advantages over compendial methods in testing ER solid oral formulations.

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR LIMIT OF N-NITROSODIMETHYLAMINE BY LC-MS/MS OF EMPAGLIFLOZIN, LINAGLIPTIN AND METFORMIN HCL EXTENDED-RELEASE TABLETS

As a result of the devotion of The Limit of N-Nitrosodimethylamine (NDMA), a rapid and selective LC/MS/MS technique was created and validated for Empagliflozin, Linagliptin, and Metformin Hydrochloride Extended-Release Tablets. The ionization mode of Atmospheric pressure chemical ionization (APCI) was used with high-performance liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). Separation of N-Nitrosodimethylamine (NDMA) was performed on Inertsil ODS-4 (250 mm X 4.6 mm), 5μm column with a run time of 40 minutes. A mixture of Methanol and Buffer solution (630 mg of ammonium format into 1000 mL of purified water) in the ratio of (10:90, v/v) was used as the mobile phase A. A mixture of acetonitrile and methanol comprised the mobile phase B in the ratio of (50:50) % v/v. Analytes were extracted from Empagliflozin, Linagliptin, and Metformin Hydrochloride Extended-Release Tablets. According to the International council for Harmonization of technical requirement for Pharmaceuticals for Human Uses (ICH) standards, the accuracy, precision, selectivity, recovery, and stability of the method have been validated. Over a concentration range of 0.4 -3.6 ng/mL, the technique exhibited linearity. for N- Nitrosodimethylamine of Empagliflozin, Linagliptin, and Metformin Hydrochloride Extended-Release Tablets with an acceptable correlation coefficient applies (1/X2) linear regression with weights A pharmaceutical study can benefit from this method because it is simple, fast, precise, and accurate, making it ideal for pharmaceutical research.

Accidental Opioid Intoxication in Children Treated With Low Doses of Naloxone: A Case of Fentanyl Patch Exposure and a Case of Morphine Tablet Ingestion

Accidental opioid intoxication in children is a rare affection in morocco, its recognition and management must be immediate to avoid its life threatening complications. In a period of two years (September 2019 - September 2021), two cases of severe opioid intoxication in children have been admitted in the intensive care department of the children’s hospital of Rabat. The first case is a 9 years old child admitted for tonic-clonic seizures with acute respiratory distress due to Fentanyl intoxication after being exposed to a skin patch dosed 75 μg/hour, he required mechanical ventilation and was treated with a bolus of 0,8 mg of Naloxone completed with continuous infusion for 48 hours with favorable evolution and hospital release in 5 days. The second case is a 2 years 5 months old child admitted for decreased consciousness with bradypnea due to morphine intoxication after oral ingestion of 5 extended-release morphine tablets dosed 30 mg each, treated with a single bolus of 0,8 mg of Naloxone with rapid improvement.