Immediate Release Tablets Research Articles

Melt Granulation Techniques as an Alternative Manufacturing Technology for the Generic Development of Apixaban 5 mg Immediate-Release Tablets: A Case Study

Melt Granulation Techniques as an Alternative Manufacturing Technology for the Generic Development of Apixaban 5 mg Immediate-Release Tablets: A Case Study

Crushing obstacles: A case series on alternative letermovir administration in transplant recipients.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Letermovir is used primarily for cytomegalovirus (CMV) prophylaxis in select hematopoietic cell or solid organ transplant recipients. The manufacturer has provided no guidance on whether letermovir can be crushed and administered via enteral tube. This study aimed to assess whether letermovir tablets could be manipulated (eg, through crushing) for enteral tube administration. This was a retrospective, single-center review of patients who received crushed letermovir tablets administered via enteral tube for at least 7 days, between April 2018 and August 2023. Data collection focused on demographics, transplant history, treatment characteristics associated with letermovir, and diagnosis of CMV viremia or disease. Fourteen patients met the inclusion criteria for the review and received crushed letermovir for a median of 19 days (range, 7 to 42 days). All patients were on letermovir as CMV prophylaxis, the majority of whom were lung transplant recipients. On the basis of CMV serostatus at the time of transplantation, 50% of patients were classified as being at high risk and the other 50% were in the intermediate-risk category for CMV disease. One patient developed low-level viremia with a CMV viral load of 254 IU/mL. No patients developed CMV infection or disease while receiving crushed letermovir. On the basis of this case series, manipulation of letermovir immediate-release tablets was proven to be safe and effective for patients. Crushing letermovir for administration via enteral tube should be considered as an option for patients who cannot tolerate administration via the oral route.

Leucettinib-21, a DYRK1A Kinase Inhibitor as Clinical Drug Candidate for Alzheimer's Disease and Down Syndrome.

Alzheimer's disease (AD) and Down syndrome (DS) share a common therapeutic target, the dual-specificity, tyrosine phosphorylation activated kinase 1A (DYRK1A). Abnormally active DYRK1A is responsible for cognitive disorders (memory, learning, spatial localization) observed in both conditions. In DS, DYRK1A is overexpressed due to the presence of the DYRK1A gene on chromosome 21. In AD, calcium-activated calpains cleave full-length DYRK1A (FL-DYRK1A) into a more stable and more active, low molecular weight, kinase (LMW-DYRK1A). Genetic and pharmacological experiments carried out with animal models of AD and DS strongly support the idea that pharmacological inhibitors of DYRK1A might be able to correct memory/learning disorders in people with AD and DS. Starting from a marine sponge natural product, Leucettamine B, Perha Pharmaceuticals has optimized, through classical medicinal chemistry, and extensively characterized a small molecule drug candidate, Leucettinib-21. Regulatory preclinical safety studies in rats and minipigs have been completed and formulation of Leucettinib-21 has been optimized as immediate-release tablets. Leucettinib-21 is now undergoing a phase 1 clinical trial (120 participants, including 12 adults with DS and 12 patients with AD). The therapeutic potential of DYRK1A inhibitors in AD and DS is presented.

Comparative study between the Full Factorial, Box–Behnken, and Central Composite Designs in the optimization of metronidazole immediate release tablet

The purpose of this paper is to summarize the fundamentals, benefits and limitations of various models of Design of Experiments (DoE) such as 2-Level Full Factorial Design, Central Composite Design (CCD), and Box–Behnken Design (BBD) while establishing a comparison between these models by taking the Metronidazole immediate release (IR) tablets as a case study. Metronidazole IR tablets were prepared by wet granulation method. The Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) were selected based on literature review and prior knowledge about the formulation. Critical Material Attributes (CMA) (concentration of binder, super disintegrant, and glidant), and Critical Process Parameters (CPP) (compression of the tablets) were identified based on their risk to the CQA. Screening and optimization of the CMA were performed using DoE. From the Full Factorial Design, it was observed that the disintegration time and dissolution at 30 min were significantly influenced by the selected CMAs. These significant factors were further optimized using CCD and BBD to achieve the constraints (minimum disintegration and maximum dissolution). The levels of povidone K30, crospovidone, and magnesium stearate were optimized to 10 mg, 32 mg, and 1.6 mg respectively using CCD and BBD.

Development and Evaluation of a Cost-Effective, Carbon-Based, Extended-Release Febuxostat Tablet.

This study outlines the development of a cost-effective, extended-release febuxostat (FEB) tablet using activated charcoal as an adsorbent to enhance drug release. FEB, a BCS Class II drug, presents formulation challenges due to low solubility and high lipophilicity. We evaluated eight formulations with varying FEB-to-charcoal ratios using FTIR and DSC for physical interactions and followed USP standards for overall assessment. The optimal 1:0.25 FEB-to-charcoal ratio demonstrated a consistent 12 h zero-order release pattern. In vivo studies indicated a significantly extended plasma profile compared to immediate-release tablets. The optimal tablets demonstrated acceptable hardness and disintegration times. This innovative approach enhances patient compliance, improves bioavailability, and reduces production costs, offering a promising solution for controlled FEB delivery.

Optimization of a Twin screw melt granulation process for fixed dose combination immediate release Tablets: Differential amorphization of one drug and crystalline continuance in the other

Interest in Twin Screw Melt Granulation (TSMG) processes is rapidly increasing, along with the search for suitable excipients. This study aims to optimize the TSMG process for immediate-release tablets containing two different drugs. The hypothesis is that one poorly water-soluble drug requires amorphous conversion for improved dissolution, while the other water-soluble drug, with a higher melting point (Tm), remains more stable in its crystalline form. Ibuprofen (IBU) and Acetaminophen (APAP) were chosen as the model drug combination to test this hypothesis. Various diluents, binders, and disintegrating agents were assessed for their impact on processability, crystallinity, disintegration, and dissolution during development. The temperatures used during processing were below the Tm of all components, except for IBU. Melted IBU acted as a granulating aid in addition to the binders in the formulation, facilitating granule formation. Physicochemical analyses by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD) confirmed the complete conversion of IBU into an amorphous state and the preserved crystalline nature of APAP. Saturation solubility studies showed an improvement in IBU’s solubility by ∼ 32-fold in 0.1 N HCl. Poor tablet disintegration performance led to the addition of disintegrating agents, where osmotic agents (sorbitol and NaCl) were found to significantly enhance disintegration compared to super disintegrants. The optimized formulation showed an enhanced IBU release (∼20 %) compared to the physical mixture (∼12.5) in 0.1 N HCl dissolution studies.

Bioavailability of a novel sustained-release pellet formulation of 5-flucytosine in healthy-fed participants for use in patients with cryptococcal meningitis.

Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub-Saharan Africa. 5-flucytosine (5-FC) is a unique, brain-permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5-FC has a short plasma half-life, requiring 6-hourly oral dosing with an immediate-release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5-FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5-FC SR formulation in a single dose (2 × 3000 mg), relative to 5-FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two-period crossover study was conducted in South Africa to confirm the dose of the identified 5-FC SR formulation for a twice-daily 5-FC regimen in patients. Thirty-six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0-t) for the SR formulation (49.2 ± 10.49 μg/mL and 640.4 ± 126.4 h.μg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 μg/mL and 456.6 ± 72.8 h.μg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5-FC b.i.d. in fasting conditions is recommended.

Optimizing release properties of tablets from Spondias mombin spray-dried leaves extract using dry and melt granulation

This study aimed to investigate the efficacy of conventional dry granulation (slugging) and twin-screw melt granulation (TSMG) as downstream processing methods to enhance the technological properties, such as flowability and tabletability, of spray-dried plant extracts (SDE). A hydrophilic (Polyethylene glycol 6000-PEG) and a lipophilic binder (glyceryl dibehenate-GBE) were explored for the melt granulation process. Compression behavior and powder rheological properties of SDE and its granules were investigated. Compression analysis by in-die Heckel analysis explained the SDE's poor mechanical properties resulting in poor compact integrity in addition to the poor flow properties of the SDE. Despite the success of granulation strategies to improve the material's flowability and tabletability, the TSMG granules exhibited better performance than slugged granules. Regarding formulation, the lipophilic binder facilitated greater plastic deformation than the hydrophilic binder, enhancing the release of formulations across different profiles from controlled release, adjusting the granules quantity, to immediate-release tablets containing either brittle or plastic fillers. In conclusion, TSMG combined with a lipophilic melt binder emerged as a promising technology for overcoming the challenges of poor tabletability and modifying the release profile of ellagitannin from SDE.

Effect of a High-Fat Meal on the Pharmacokinetics of an Immediate Release Atogepant Tablet.

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine. A phase 1, open-label, single-dose, 2-period crossover study evaluated the effect of a high-fat meal on the pharmacokinetics and safety of atogepant in 20 healthy adults. Administration of atogepant 60mg immediate-release (IR) tablets under fed conditions reduced the area under the plasma concentration-time curve (AUC) from 0 to time t and from 0 to time infinity by approximately 18% and reduced the maximum plasma concentration (Cmax) by 22%. The 90% confidence intervals for the geometric mean ratios of Cmax and AUC were not contained within the bioequivalence limits of 80%-125%. There was no change in the median time to maximum plasma concentration in the fed versus fasted state. The incidence of treatment-emergent adverse events (TEAEs) was similar between fed and fasted conditions. Four TEAEs were considered related to study intervention and were reported after participants received atogepant under fasted conditions (3 participants). A single-dose atogepant 60mg IR tablet was safe and tolerated under both fed and fasted states. Due to the wide effective dose range of 10-60mg/day for atogepant for the preventive treatment of migraine, the food effect on its pharmacokinetics is not considered clinically relevant.

Formulation and Evaluation of Immediate Release Tablets of Antimalarial Drug Hydroxychloroquine

The goal of the study was to develop and evaluate an immediate-release antimalarial tablet formulation for the effective management of malaria, an antimalarial drug as an active pharmaceutical ingredient using excipients. Appropriate pharmaceutical products and evaluate their properties in relation to the innovative product. The study was to develop an antimalarial formulation with in-vitro solubility properties equivalent to or better than the improved formulation. Therefore, an orally administered immediate-release tablet with a robust and reproducible formulation technique was developed. According to the study, the number of F3 definitions decreased the most and F8 had the most important medicinal properties. At 20 minutes, F4 appeared to lead the first high decay rate (98. 56%), followed closely by F5 (93.48%). The expansion of F1, F2 and F3 shows high decay rates at this time. Based on this information, one can analyze and compare the decay profiles of unmistakable definitions. Things such as composition, excipients used, and manufacturing geometry can influence degradation behavior, and this information may be necessary to optimize concentrations of substances of interest for drug delivery. It is then concluded that the definition number F5 may be an optimized detail.

Qualification of In Vitro Dissolution Absorption System 2 (IDAS2) with Caco-2 and MDCK Cell Monolayers: Dose Sensitivity Study Using BCS Class I and III Drugs.

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.

Forecasting the effect of water gastric emptying patterns on model drug release in an in vitro glass-bead flow-through system.

Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.

P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and Japanese Participants.

Afferent neuronal hypersensitization via P2X3 receptor signaling has been implicated as a driver of several disorders, including refractory chronic cough, endometriosis, diabetic neuropathic pain, and overactive bladder. Eliapixant, a selective P2X3 receptor antagonist, has been in clinical development for all four disorders. This paper describes pharmacokinetic (PK) and safety data from two phase I studies of eliapixant in healthy Japanese and Chinese participants and compares those data within the two populations and with previous multiple dose data from Caucasian participants. Two separate phase I, single-center, randomized, placebo-controlled studies were conducted with healthy male participants. The Japanese study was single-blind and the Chinese study was double-blind. Eliapixant was administered as an oral amorphous solid dispersion immediate-release tablet in strengths of 25 mg, 75 mg, and 150 mg. PK characteristics after a single dose (SD) and at steady state (multiple dose [MD], twice daily), adverse events (AEs), and tolerability were evaluated. A post hoc comparison of PK characteristics after SD of eliapixant in Japanese and Chinese participants, and after MD of eliapixant in Japanese, Chinese, and Caucasian participants, was performed. Overall, 36/39 participants enrolled in the Japanese/Chinese studies, respectively (mean [standard deviation] age 25.4 [6.5] and 26.7 [5.0] years, respectively). After SD administration, maximum plasma concentration (Cmax) was higher among Japanese than Chinese participants in the 25 mg and 75 mg dose groups, but comparable in the 150 mg dose group. The area under the concentration-time curve (AUC) was comparable between Japanese and Chinese participants in the 25 mg and 75 mg dose groups, but lower among Japanese participants in the 150 mg group. Half-lives after SD and MD administration were also comparable in Japanese and Chinese participants. The post hoc analysis included 26 Japanese, 30 Chinese, and 50 Caucasian participants. Comparable exposure (Cmax,md and AUC[0-12]md) was observed after MD administration of eliapixant in Chinese and/or Japanese compared with Caucasian participants (geometric mean inter-ethnic ratios close to 1). The trough plasma concentration after eliapixant 150 mg MD, which was assumed to be relevant to eliapixant efficacy, was comparable across all ethnicity groups. Most AEs reported in the Japanese (eliapixant 75 mg SD, n = 2; eliapixant 150 mg MD, n = 2) and Chinese participants (eliapixant 25 mg SD, n = 7; eliapixant 75 mg SD, n = 6; eliapixant 150 mg SD, n = 7; eliapixant 150 mg MD, n = 9; placebo SD, n = 5; placebo MD, n = 1) were of mild intensity. Higher incidences of AEs in the Chinese population were likely due to differing standards of AE reporting between investigators. Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants. ClinicalTrials.gov identifier numbers: NCT04265781 and NCT04802343.

Preparation and Evaluation of Metronidazole Tablets Produced with Different Binders Using Wet Granulation Method

In tablet formulation, binders are essential for ensuring proper powder mix, granulation and overall tablet quality. Variations in binder quality and concentration can impact drug bioavailability, strength and manufacturing processes. The inconsistency in bioavailability and therapeutic response of metronidazole from different manufacturers highlights the importance of binder selection in tablet formulation. This study evaluates the impact of different binding agents on tablet quality. The optimum binder concentration for each of the binders was assessed to obtain suitable concentration that was used to prepare metronidazole tablets. Metronidazole tablets were formulated with four different binder vis, acacia, gelatine, PVP, maize starch at 3% concentration using wet granulation method after which the tablet properties were evaluated. Metronidazole powder exhibited poor flow indices, as indicated by angle of repose: 39.92 ± 1.85, Carr’s compressibility index (CI): 20.13 ± 0.28 and Hausner’s ratio (Hr): 1.26 ± 0.01, whereas its granules exhibited good flow properties. The crushing strength (CS), friability (FR), disintegration time (DT) (CSFR/DT) ratio for batches showed values in 3% binder concentration, indicating higher strength as compared to other concentrations. There was a significant increase (P < 0.05) in the CSFR/DT ratio for gelatine (2.22) in formulation F2 compared to maize starch in Formulation F4. The formulated tablets with the various binders have met with the British Pharmacopeial criteria of 80% drug release from uncoated immediate-release tablets. Amongst the four binders, gelatine was found to be the best in the formulation of robust metronidazole tablets by wet granulation method at an optimised concentration of 3% w/w. Tablets produced with gelatin exhibited greater mechanical strength than those produced with other binders, while also demonstrating a slightly longer DT. Metronidazole tablets produced with gelatine have met the British Pharmacopeial requirements including an acceptable in-vitro drug release profile.

Integrating Clinical Variability into PBPK Models for Virtual Bioequivalence of Single and Multiple Doses of Tofacitinib Modified-Release Dosage Form.

Tofacitinib is a potent, selective inhibitor of the Janus kinase (JAK) family of kinases with a high degree of selectivity within the human genome's set of protein kinases. Currently approved formulations for tofacitinib citrate are immediate-release (IR) tablets, modified-release (MR) tablets, and IR solution. A once daily MR microsphere formulation was developed for use in pediatric patients. Demonstration of bioequivalence (BE) between the 10 mg once daily (q.d.) MR microsphere formulation and 5 mg twice daily (b.i.d.) IR solution is needed to enable the exposure-response analyses-based bridging to support regulatory approval. To assess BE between MR microsphere and IR solution, an innovative approach was utilized with physiologically-based pharmacokinetic (PBPK) virtual BE trials (VBE) in lieu of a clinical BE trial. A PBPK model was developed to characterize the absorption of different formulations of tofacitinib using Simcyp ADAM module. VBE trials were conducted by simulating PK profiles using the verified PBPK model and integrating the clinically observed intrasubject coefficient of variation (ICV) where BE was assessed with a predetermined sample size and prespecified criteria. The VBE trials demonstrated BE between IR solution 5 mg b.i.d. and MR microsphere 10 mg q.d. after a single dose on day 1 and after multiple doses on day 5. This research presents an innovative approach that incorporates clinically observed ICV in PBPK model-based VBE trials, which could reduce unnecessary drug exposure to healthy volunteers and streamline new formulation development strategies.

Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug

Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such as the Magenstrasse or chyme areas of different pH and viscosity, play an important role in the intragastric drug dissolution and its transfer to the intestine. In this study, we investigated the data gathered in the bioequivalence trial between an immediate-release tablet (Reference) and an orally dispersible tablet (Test) with a poorly soluble weak base drug administered with or without water after a high-fat high-calorie breakfast. Maximum concentrations (Cmax) were significantly greater after administering the Reference product than the Test tablets, despite similar in vitro dissolution profiles. To explain this difference, we constructed a novel semi-mechanistic IVIVP model including a heterogeneous gastric chyme. The drug dissolution in vivo was modeled from the in vitro experiments in biorelevant media simulating gastric and intestinal fluids in the fed state (FEDGAS and FeSSIF). The key novelty of the model was separating the stomach contents into two compartments: isolated chyme (the viscous food content) that carries the drug slowly, and aq_chyme open for rapid Magenstrasse-like routes of drug transit. Drug distribution between these two compartments was both formulation- and administration-dependent, and recognized the respective drug fractions from the clinical pharmacokinetic data. The model’s assumption about the nonuniform mixing of the API with the chyme, influencing differential drug dissolution and transit kinetics, led to simulating plasma concentration profiles that reflected well the variability observed in the clinical trial. The model indicated that, after administration, the Reference product mixes to a greater extent with aq_chyme, where the released drug dissolves better and transfers faster to the intestine. In conclusion, this novel approach underlines that diverse gastric emptying of different oral dosage forms may significantly impact pharmacokinetics and affect the outcomes of bioequivalence trials.

Development and assessment of immediate-release tablets containing clopidogrel bisulphate & aspirin-strategy for optimizing the combination formulation.

The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin's stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.

Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Formulation and Evaluation of Immediate-Release Oral Tablets Containing Magnesium Aluminum Silicate-Loaded Simvastatin

Background: Simvastatin (SIM) is a lipid-lowering agent to prevent disorders caused by clogged blood vessels. Because of its low solubility, it has low bioavailability. The adsorption technique is effective in improving drug solubility and dissolution rate. Objective: To use magnesium aluminum silicate (MAS) as an adsorbent in combination with Soluplus® as a hydrophilic polymer to formulate SIM as immediate-release tablets (IRTs). Methods: We used the solvent evaporation method to make MAS-loaded SIM in the presence of Soluplus®, making sure that the ratio of SIM to MAS to SOLU was 1:6:3. We then used this mixture to make IRTs. Using the direct compression method, we made all of the SIM-IRT formulas. We used diluents like Avicel®PH102, Avicel®PH101, and starch, as well as super disintegrants like Crospovidone (CP), Croscarmellose sodium (CCS), and sodium starch glycolate (SSG). We evaluated these formulas for their weight variation, hardness, friability, disintegration time, drug content, and dissolution profile. Results: We prepared the tablet formula (T5) using MAS-loaded SIM, Avicel®PH102 as a diluent, and CCS 3% as a super disintegrant. This formula showed the shortest disintegration time (0.61 min) and best drug release in phosphate buffer pH 7.0, releasing more than 80% of the drug within 30 minutes. Conclusion: Using suitable excipients, adsorption was an efficient method to enhance the solubility of SIM for preparation as IRTs.

Tablets containing açaí (Euterpe spp.) dried extract for dietary supplementation: A study of functional properties

Açaí is a very popular functional food in the Amazon due to its nutritional properties, its high caloric value, and its high content of anthocyanins and phenolic compounds, which mainly confers antioxidant and anti-inflammatory activities. Thus, this study aimed at the development of immediate-release tablets containing açaí dried extract by direct compression. The extract was subjected to physical evaluation of the powder, quantification of total polyphenol (TP) content (mg EAG/g), total anthocyanin content (mg C3G/100 g), cyanidin-3-rutinoside marker (µg C3R/g) by LC-MS, obtention of the tablet, and their physical-mechanical evaluation. Açaí dried extract showed spherical shape particles, with smooth and rough surfaces and heterogeneous sizes, which are characteristic of dried powders when obtained by spray drying. In addition, the extract presented TP content (23.307± 2.190 mg EAG/g), total anthocyanins (10.52 mg C3G/100 g), and cyanidin-3-rutinoside (42 µg C3R/g). Tablets had good mechanical properties, good thermal stability under 200°C, and 3.65 µg C3R/g of cyanidin-3-rutinoside content per tablet unit. The results obtained in this study showed the possibility of obtaining tablets containing açaí dried extract with good mechanical properties and antioxidant activity aiming its use as a dietary supplement.