Solid Dispersion Tablets Research Articles

Investigating the effects of formulation variables on the disintegration of spray dried amorphous solid dispersion tablets

Amorphous solid dispersion (ASD) tablets based on hydrophilic polymer carriers may encounter disintegration challenges. In this work, the effect of different formulation composition variables on the ASD tablet disintegration performance was systematically studied. GDC-0334: copovidone (PVPVA) 60: 40 ASD prepared by spray drying was selected as the model ASD system. The effects of ASD loading, filler type and ratio, disintegrant type and level were then investigated using tablets made by direct compression process. Tablet disintegration time increased with the increase of ASD loading, especially when ASD loading exceeded 50 %. At the same tablet solid fraction, when lactose was used as the soluble filler, faster tablet disintegration time was observed compared to the tablets with mannitol as the soluble filler. Among the three tested disintegrants, croscarmellose sodium performed the best in facilitating the ASD tablet disintegration, followed by sodium starch glycolate, and crospovidone was the poorest. When croscarmellose sodium was used as the disintegrant, 5 % level was sufficient to enable ASD tablet disintegration at 60 % ASD loading and further increase of croscarmellose sodium level to 8 % did not provide additional benefit. Water uptake experiments were performed on selected tablets and the results demonstrated a positive correlation with tablet disintegration time, indicating water penetration is a major contributing step for the disintegration of our ASD tablets. Overall, this work provides a rationale for excipient selection and insights into building a platform formulation approach for developing immediate-release ASD tablets.

Enhanced Oral Bioavailability and Stability Studies of Loratadine Tablets Based on Solid Dispersion of Modified Ziziphus spina-christi Gum

Background: Solid dispersion is a common technique used for solubility enhancement of poorly soluble drugs. Objective: In this study, loratadine (LOR), a class II biopharmaceutical classification system (BCS), was formulated as solid dispersion tablets using modified Ziziphus spina-christi gum (MZG) as a carrier. Methods: The solvent evaporation method was used for LOR-MZG solid dispersion (SD) preparation. A variety of tests were conducted to characterize and optimize the formulation. Solubility, Fourier transform infrared (FTIR) analysis, Differential Scanning Calorimetry (DSC), X-Ray Diffraction (X-RD), and Scanning Electron Micrograph (SEM) of solid dispersions were carried out. Accelerated stability testing and pharmacokinetic studies of formulated tablets were also performed using albino Wistar rats. Results: Solid dispersion improved the solubility of LOR by 51 folds. FTIR spectra excluded drugpolymer interactions, and results obtained by DSC, X-RD, and SEM proved the transition from the crystalline to the amorphous state. The stability of LOR-MZG solid dispersion tablets was found to be better when the Alu-Alu package was used. The pharmacokinetics of LOR-MZG compared to MZG-free loratadine tablets (LOR pure) and commercial loratadine tablets (LOR-TM) following oral administration revealed that about 6 folds and 10 folds bioavailability were achieved with LOR-MZG compared to LOR pure and LOR-TM, respectively. Conclusion: Such promising results encourage more studies on MZG to be used for improving the aqueous solubility and bioavailability of a wide range of poorly soluble drugs.

Design and Characterization of Fast Dissolving Solid Dispersion Tablets of Gliclazide

Design and Characterization of Fast Dissolving Solid Dispersion Tablets of Gliclazide

Formulation and Evaluation of Tablets Using the Solvent Evaporation Method to Increase the Solubility of Lansoprazole

The inability to determine sufficient and repeatable bioavailability and/or desirable pharmacokinetic features in humans is one of the biggest obstacles to the oral administration of new medicines. The solubility and absorption of a medicine determine its bioavailability, which in turn determines its therapeutic efficacy. Achieving the target drug concentration in the systemic circulation and ensuring drug biological activity in humans are both affected by solubility. A stomach ulcer has the potential to rip through the stomach lining, the initial section of the small intestine, and possibly even the lower esophagus. Distinct ulcers form in different parts of the intestines; one forms in the duodenum and one in the stomach. Duodenal ulcers are most commonly characterized by upper abdominal pain at night that subsides after eating. Eating might exacerbate the discomfort from a stomach ulcer. Preparing and assessing the pills will yield optimal outcomes. The active component content is 99.90%, as is the active ingredient release rate. Compared to other formulations, solid dispersion tablets performed better in in-vitro tests (98.85%). The optimized formulation (lansoprazole solid dispersion tablets) outperformed the labeled formulation (conventional lansoprazole tablet) in terms of drug-releasing capacity within 6 hours, outperforming both formulations.

Dissolution enhancement of Gefitinib by solid dispersion and complexation with β-cyclodextrins: In vitro testing, cytotoxic activity, and tablet formulation

Cancer is the leading cause of mortality worldwide. In patients with metastatic non-small cell lung cancer, epidermal growth factor receptor (EGFR) is often overexpressed. Gefitinib (GEF), an inhibitor of EGFR, is approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the low solubility and dissolution of GEF limits its bioavailability. Numerous methods, including solid dispersion (SD) and complexation, have been reported to enhance the dissolution of poorly soluble drugs. In this study, GEF complexes were prepared using methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) in two molar ratios (1:1 and 1:2), furthermore, GEF SDs were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188(PXM) in three different ratios (1:2, 1:4 and 1:6 w/w). Dissolution studies were conducted on the prepared formulations. Dissolution results showed a 1.22–2.17-fold enhancement in drug dissolution after one hour compared to untreated GEF. Two formulations that showed higher dissolution enhancement were subsequently evaluated for in-vitro cytotoxicity and were formulated into tablets. The selected PVP–GEF (1:4 w/w) and MβCD–GEF (1:1M) formulas displayed improved cytotoxicity compared to untreated GEF. The IC50 values of the PVP–GEF and MβCD–GEF were 4.33 ± 0.66 and 4.84 ± 0.38 µM, respectively which are significantly lower (p < 0.05) than free GEF. In addition, the formulated tablets exhibited enhanced dissolution compared to pure GEF tablets. PVP–GEF SD tablets released (35.1 %±0.4) of GEF after one hour, while GEF-MβCD tablets released (42.2 % ± 0.7) after one hour. In the meantime, tablets containing pure GEF showed only 15 % ± 0.5 release at the same time. The findings of this study offer valuable insights for optimizing the dissolution and hence therapeutic capabilities of GEF while mitigating its limitations.

Formulation and Evaluation of Solid Dispersion of Felodipine by Hot Melt Extrusion for Enhancement of Solubility

ABSTRACT Background: Felodipine (BCS Class II) undergoes extensive first-pass metabolism with bioavailability of about 15% that creates problem in therapeutic efficacy after oral administration. Objective: Immediate release formulation of felodipine was developed using hot-melt extrusion (HME) technique in an attempt to improve solubility and dissolution of felodipine through the solid dispersion technique. Materials and Methods: The solid dispersion was prepared using Eudragit EPO, NE30D as a carrier with different drug polymer ratios using the HME technique. The optimized batch was made into tablets. The solid dispersion was characterized by solubility studies, drug content, and in vitro dissolution rate studies. Results: From the cumulative dissolution profile, it was observed that the drug and Eudragit EPO alone have the highest percentage of drug release compared to the other combinations of drug and Eudragit EPO, NE30D. It is also evident from the dissolution profile that with increase in the concentration of Eudragit NE30D, there is a decrease in the dissolution rate. There was a significant decrease in drug release even with increase in stabilizer in a smaller ratio. The dissolution profile showed that there is not much variation in the release profile of the solid dispersion alone and the solid dispersion tablets. Conclusions: Solid dispersion by the HME technique is an effective method to increase the dissolution rate of felodipine.

The impact of diluents on the compaction, dissolution, and physical stability of amorphous solid dispersion tablets

Amorphous solid dispersion (ASD) is an effective approach for enhancing the solubility, dissolution, and bioavailability of poorly water-soluble drugs. However, these metastable forms can transform into more thermodynamically stable but less soluble crystalline forms. Despite this challenge, research on processing ASDs into solid dosage forms, such as tablets, is lacking. This work aims to fill this gap by investigating the impact of common diluents on the tableting behavior, dissolution, and physical stability of ASDs composed of itraconazole and hypromellose acetate succinate. Four widely used diluents found in commercially available ASD tablets were selected for the study: microcrystalline cellulose (MCC), anhydrous lactose, starch, and mannitol. The performance of ASD tablets varied significantly depending on the diluent used. Tablets prepared with MCC exhibited higher mechanical strength than those formulated using other diluents. ASD tablets containing mannitol and lactose revealed a faster release rate than those composed of MCC or starch. Notably, the study highlighted that the physical stability of ASDs within a tablet is not solely dependent on the amount of sorbed water; crystalline diluents like lactose and mannitol were found to facilitate ASD recrystallization within a tablet. In summary, the study underscores the importance of excipient selection, considering factors such as mechanical strength, dissolution rate, and physical stability of ASD tablets. These findings offer valuable insights into the selection of excipients for downstream ASD tablet development, leading to improved manufacturability, physical stability, and the overall quality of ASD drug products.

Formulation, Development, and Evaluation of Bosentan Monohydrate Spray Dried- Solid Dispersion Tablets for Improved Dissolution Profile

Bosentan monohydrate (BM) is utilized for the treatment of pulmonary arterial hypertension, exhibiting poor aqueous solubility and bioavailability. This study aims to enhance the dissolution rate of the drug using Eudragit®EPO through spray drying. The drug and Eudragit®EPO were combined in ratios of 1:1, 1:2, 1:3, 1:4, and 1:5 (w/w) to generate compositions SD1 to SD5. SD5, at a 1:5 drug-to-carrier ratio, demonstrated a statistically significant increase in saturation solubility and drug content. Six tablet formulations (F1 to F6) containing SD5 and tableting excipients were developed and processed. Formulation F2, consisting of 26.36% HPMC K4M and 23.63% MCC, exhibited the highest dissolution and drug release. The probable mechanism underlying BM dissolution in SD involves its amorphous form and the solubilizing effect facilitated by hydrogen bonding between BM and Eudragit®EPO. The carrier's binding effect likely contributed to high tensile strength, low friability, and extended disintegration time. Direct mixing of SD with HPMC might have improved the uniformity of SD within the tablet matrix and the release profile. This study demonstrates the efficacy of spray drying in preparing SD of BM with Eudragit®EPO, potentially enhancing its solubility and stability.

Preparation and evaluation of ciprofloxacin solid dispersion tablets developed from stearic acid, Polyethylene Glycol 4000 and Soluplus

Ciprofloxacin is a fluoroquinolone antibiotic with a broad spectrum of activity used for the treatment of various bacterial infections and is characterized by poor aqueous solubility and low permeability. The aim of this study is to formulate and characterize ciprofloxacin solid dispersions using hydrophilic and lipophilic matrices for improved product qualities and drug delivery. Ciprofloxacin hydrochloride tablets were formulated as solid dispersions by melting and solvent evaporation in tablet moulds using varying concentrations of stearic acid (10-40 %w/w), Polyethylene glycol 4000 (PEG 4000) (10-40 %w/w) and Soluplus® (10-20 %w/w as ethanolic solution) as components. The prepared tablets were evaluated for weight uniformity, friability, hardness, Fourier transform-infrared spectroscopy (FT-IR), moisture uptake, swelling index, disintegration time and dissolution rate, using standard methods and optimization techniques. The results showed uniform solid dispersion weights with friability, hardness, moisture uptake and swelling index of 0.4-0.5%, 3.0-7.5 kgf, mostly &lt;20% and 1-71%, respectively. The formulations were chemically stable with no transformational interactions between components. Formulations without stearic acid disintegrated within 30 min whereas those containing the lipid broke up after more than 1 h. Drug release studies showed high immediate release in tablets without stearic acid but with cumulative steady state release higher in formulations with 10 %w/w Soluplus and different concentrations of stearic acid and PEG 4000. In conclusion, ciprofloxacin was presented as solid dispersion tablets with modified physicochemical attributes for improved drug delivery.&#x0D; Keywords: Ciprofloxacin; solid dispersion; drug delivery

Micro-Injection Moulding of PEO/PCL Blend–Based Matrices for Extended Oral Delivery of Fenbendazole

Fenbendazole (FBZ) is a broad-spectrum anthelmintic administered orally to ruminants; nevertheless, its poor water solubility has been the main limitation to reaching satisfactory and sustained levels at the site of the target parasites. Hence, the exploitation of hot-melt extrusion (HME) and micro-injection moulding (µIM) for the manufacturing of extended-release tablets of plasticised solid dispersions of poly(ethylene oxide) (PEO)/polycaprolactone (PCL) and FBZ was investigated due to their unique suitability for semi-continuous manufacturing of pharmaceutical oral solid dosage forms. High-performance liquid chromatography (HPLC) analysis demonstrated a consistent and uniform drug content in the tablets. Thermal analysis using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the amorphous state of the active ingredient, which was endorsed by powder X-ray diffraction spectroscopy (pXRD). Fourier transform infrared spectroscopy (FTIR) analysis did not display any new peak indicative of either a chemical interaction or degradation. Scanning electron microscopy (SEM) images showed smoother surfaces and broader pores as we increased the PCL content. Electron-dispersive X-ray spectroscopy (EDX) revealed that the drug was homogeneously distributed within the polymeric matrices. Drug release studies attested that all moulded tablets of amorphous solid dispersions improved the drug solubility, with the PEO/PCL blend-based matrices showing drug release by Korsmeyer-Peppas kinetics. Thus, HME coupled with µIM proved to be a promising approach towards a continuous automated manufacturing process for the production of oral solid dispersions of benzimidazole anthelmintics to grazing cattle.

Solubility enhancement of antiprotozoal agent by solid dispersion and herbal tablet method to improve its rate of dissolution

Drug dissolution is the rate limiting step for bioavailability of poor aqueous soluble drug that consequently affects the in vivo drug absorption. In the present study solid dispersion based drug delivery system of Atovaquone were successfully developed in the form of tablets with improved dissolution characteristic by forming solid dispersion with PEG 4000. For the Atovaquone formulation, F1 was chosen as it has % drug release about 46 % in 180 min. FTIR spectra of drug with other excipients have not shown any interaction and also selected formulation was stable after stability studies. The in-vitro dissolution studies revealed a considerable boost in dissolution rate of Solid dispersions of Atovaquone in contrast to pure drug. From FTIR spectroscopy, it was concluded that there was no well-defined chemical interaction between Atovaquone and PEG 4000 in Solid dispersions, as no important new peaks could be observed. The Atovaquone solid dispersion based tablet (F1) showed 30.33% drug release within first 20 min. and 46.45% drug release within 180 min.Thus from studies, it could be concluded that solid dispersion of poor aqueous soluble Atovaquone by solvent evaporation technique were effectively formulate during PEG-4000 and PVP-K 30 hydrophilic polymers. Thus, the statement can be given that the rate of dissolution and solubility of poor aqueous soluble Atovaquon can be appreciably improved by solid dispersion by use of water soluble carriers by solvent evaporation technique.

Itraconazole Amorphous Solid Dispersion Tablets: Formulation and Compaction Process Optimization Using Quality by Design Principles and Tools.

BCS Class II drugs, such as itraconazole (ITZ), exhibit poor solubility (1-4 ng/mL) and so require solubility enhancement. Therefore, ITZ and Kollidon® VA64 (KOL) amorphous solid dispersions (ASDs) were produced using hot-melt extrusion (HME) to improve ITZ's poor solubility. A novel strategy for tablet formulations using five inorganic salts was investigated (KCl, NaCl, KBr, KHCO3 and KH2PO4). These kosmotopric salts are thought to compete for water hydration near the polymer chain, hence, preventing polymer gelation and, therefore, facilitating disintegration and dissolution. Out of all the formulations, the KCl containing one demonstrated acceptable tensile strength (above 1.7 MPa), whilst providing a quick disintegration time (less than 15 min) and so was selected for further formulation development through a design of the experiment approach. Seven ITZ-KOL-ASD formulations with KCl were compacted using round and oblong punches. Round tablets were found to disintegrate under 20 min, whereas oblong tablets disintegrated within 10 min. The round tablets achieved over 80% ITZ release within 15 min, with six out of seven formulations achieving 100% ITZ release by 30 min. It was found that tablets comprising high levels of Avicel® pH 102 (30%) and low levels of KCl (5%) tend to fail the disintegration target due to the strong bonding capacity of Avicel® pH 102. The disintegration time and tensile strength responses were modeled to obtain design spaces (DSs) relevant to both round and oblong tablets. Within the DS, several formulations can be chosen, which meet the Quality Target Product Profile (QTPP) requirements for immediate-release round and oblong tablets and allow for flexibility to compact in different tablet shape to accommodate patients' needs. It was concluded that the use of inorganic salts, such as KCl, is the key to producing tablets of ITZ ASDs with fast disintegration and enhanced dissolution. Overall, ITZ-KOL-ASD tablet formulations, which meet the QTPP, were achieved in this study with the aid of Quality by Design (QbD) principles for formulation and compaction process development and optimization.

용해도가 개선된 엔잘루타마이드 고체분산체 함유 정제의 개발

The objective of this study was to develop a novel enzalutamide tablet formulation with enhanced solubility and bioavailability, and inhibited recrystallization. Kollidon VA64 was selected as a soluble polymer for preparing enzalutamide solid dispersions. Solid dispersions with different enzalutamide to Kollidon VA64 weight ratios were prepared via solvent evaporation method. The enzalutamide solid dispersion consisting of enzalutamide and Kollidon VA64 at a weight ratio of 1:1, exhibited an excellent dissolution rate and potent inhibition of recrystallization. Enzalutamide solid dispersions were characterized by scanning electron microscopy, powder X-ray diffractometry, differential scanning calorimetry, and in vitro dissolution studies. The 1:1 solid dispersion exhibited excellent productivity, an elevated dissolution rate, and recrystallization inhibition. Therefore, enzalutamide solid dispersion loaded tablets were prepared and their dissolution was evaluated compared to a commercial product (Xtandi® soft capsule). The selected tablet formulation containing enzalutamide solid dispersion exhibited a higher dissolution rate in pH 1.0 solution than did the Xtandi® soft capsule, and prevented recrystallization of the enzalutamide. This research suggests that enzalutamide-containing solid dispersion tablets could be the most effective method to date for improving the dosing compliance of Xtandi® soft capsules, improving the dissolution rate of enzalutamide, and preventing recrystallization.

Surface Characterization as a Tool for Identifying the Factors Affecting the Dissolution Rate of Amorphous Solid Dispersion Tablets.

An amorphous solid dispersion (ASD) is a commonly used approach to enhancing the dissolution of poorly aqueous soluble drugs. Selecting the desired polymer and drug loading can be time-consuming. Surface properties, such as surface composition and wetting behavior, are essential factors controlling the dissolution of ASD tablets. Thus, our study aims to use surface characterization to understand the factors that affect the dissolution rate of ASD tablets. In this work, we prepared ASDs with itraconazole and hypromellose acetate succinate (HPMCAS) using spray drying. ASDs were prepared using three grades of HPMCAS and different drug loading levels (10%, 30%, and 50%). We prepared ASD tablets with two porosities. For each tablet, contact angles were measured using the Drop Shape Analyzer; surface free energies, disperse, and polar fractions were calculated based on the contact angles. We conducted near-infrared (NIR) and dissolution measurements of ASD tablets. Principal component analysis (PCA) was carried out to investigate the NIR spectra further. The relative PCA scores were reported with other sample properties. A partial least square (PLS) model using NIR scores, tablets' wetting properties, and dissolution rates revealed that water and buffer contact angles, surface free energy, and polar fraction are the most significant factors attributing to the dissolution rate of ASD tablets. This work understood the interplay between the surface properties and the dissolution rate of ASD tablets. Moreover, surface characterization can be the tool to screen the formulation and compaction process of ASD tablets in early development.

Formulation and evaluation of fast dissolving tablets of haloperidol solid dispersion

PurposeThe aim of this study was to design fast dissolving tablets (FDT) of the anti –psychiatric drug haloperidol in solid dispersion forms as a way to enhance its dissolution profile and anti-psychiatric effect. MethodsSolubility studies of haloperidol in various polymers solutions were investigated. The selected polymer with high drug solubility (Poly ethylene glycol 4000) was used for preparation of solid dispersion through two methods solvent evaporation method and melting method. Haloperidol solid dispersion mixed with other solid powder excipients and compressed into tablets. The resulted tablets were evaluated according to British Pharmacopoeia (B.P.) specifications. Pre- and post -compression studies were performed to determine the flow properties and evaluate the solid dispersion systems, followed by in vivo studies through forced swimming test (FST) ResultsPre-compression studies showed adequate flowability and compatibility of polymer and solid excipients with haloperidol. The selected solid dispersion tablet (SD2) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. Attempts of in vitro dissolution results and thermodynamic stability studies showed acceptable results for (SD2) formulation containing PEG 4000 polymer prepared by melting method.The in vivo study of (SD2) formulation revealed the highest immobility time to rats compared to control rats and others treated with commercial haloperidol product. ConclusionFast dissolving tablets prepared from solid dispersion of haloperidol with PEG4000 expressed rapid onset of action with enhanced anti-psychiatric effect of haloperidol.

Biopredictive capability assessment of two dissolution/permeation assays, µFLUX™ and PermeaLoop™, using supersaturating formulations of Posaconazole

The majority of new drug entities exhibits poor water solubility and therefore enabling formulations are often needed to ensure sufficient in vivo bioavailability upon oral administration. Several in vitro tools have been proposed for biopredictive screening of such drug formulations to facilitate formulation development. Among these, combined dissolution/permeation (D/P) assays have gained increasing interest in recent years, since they are presumed to better predict the absorption behavior as compared to single-compartment dissolution assays. Moreover, especially for supersaturating formulations, it has been demonstrated that the presence of an absorption sink better mimics the intraluminal supersaturation performance.The present study aimed to investigate the biopredictive abilities of two in vitro D/P setups to predict intestinal supersaturation and systemic absorption of supersaturable systems. Experiments were performed with a µFLUX™ and PermeaLoop™ apparatus, respectively, which differ primarily in their volume-to-area ratios between donor compartment and membrane as well as in the type of biomimetic barrier. A two-stage dissolution protocol was adopted to mimic the transit from acidic stomach to more neutral intestinal fluids using biomimetic media. Three formulations of the weakly basic compound Posaconazole (PCZ), namely an acidified and a neutral suspension and an amorphous solid dispersion (ASD) tablet, were tested.Under the present conditions, and for the specific set of formulations studied here, PermeaLoop™ showed a better biopredictive ability for intestinal supersaturation and systemic absorption for the three formulations than the µFLUX™ D/P setup. Interestingly, minor modifications of the two-stage D/P protocol in terms of medium transfer rates from simulated gastric fluid (SGF) to fasted state simulated intestinal fluid (FaSSIF) had a substantial impact particularly on the permeation of the crystalline PCZ suspension (“acidified suspension”). The ASD tablet was less sensitive to gradual medium changes than the crystalline PCZ suspensions. The current study confirms the usefulness of D/P assays for formulation ranking of weakly basic compounds and supersaturating formulations.

Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials

Cirrhosis-related complications are a major burden. Rifaximin soluble solid dispersion (SSD) tablets (immediate-release [IR]; sustained extended-release [SER]) were designed to increase rifaximin water solubility. These analyses evaluate dosing for prevention of cirrhosis complication-related hospitalizations/mortality and overt hepatic encephalopathy (OHE) treatment. Two phase II, randomized, double-blind, placebo-controlled trials were conducted. Trial 1: outpatients with early decompensated cirrhosis randomized to placebo or rifaximin SSD once-nightly: IR 40 or 80 mg, SER 40 or 80 mg, or IR 80 mg plus SER 80 mg, for 24 weeks. Trial 2: inpatients with OHE randomized to lactulose plus placebo or rifaximin SSD: IR 40 mg once or twice daily or SER 80 mg once or twice daily for ≤14 days. Primary efficacy endpoint: time to cirrhosis complication-related hospitalization/all-cause mortality (Trial 1) or time to OHE resolution (Trial 2). In Trial 1 (n= 516), no significant difference in time to cirrhosis complication-related hospitalization/all-cause mortality vs placebo. In a post hoc analysis, time to all-cause hospitalization/all-cause mortality was improved with IR 40 mg vs placebo (15.4% [12/78] vs 27.7% [26/94]; P= .03). A Trial 2 prespecified interim analysis (n= 71) showed lactulose plus rifaximin SSD IR 40 mg bid significantly reduced median time to OHE resolution (21.1 hours) vs lactulose plus placebo (62.7 hours; P= .02). Trial 2 was subsequently terminated. Rifaximin SSD IR 40 mg may reduce hospitalizations in patients with cirrhosis and shorten duration of OHE during hospitalization-considered a negative finding, yetalso hypothesis-generating. (ClinicalTrials.govNCT01904409; NCT03515044).

SOLID DISPERSION TABLETS IN IMPROVING ORAL BIOAVAILABILITY OF POORLY SOLUBLE DRUGS

Recent advances in the field of conversion of solid dispersions of poorly water-soluble drugs in a wide range of hydrophilic or water-soluble carriers into solid dispersion tablets have shown great promise in improving solubility, dissolution rate and oral bioavailability of such drugs. Moreover, proper choice of tablet excipients during tableting of optimised solid dispersions can produce either fast/rapid or sustained drug release profile. Release kinetics have been found to follow either first-order kinetics or Higuchi model and release profiles in most of the cases have been found to be superior to that of conventional tablets or capsules. The present review aims to sum up the various studies on solid dispersion tablets and establish the novelty of this unique approach in the overall improvement of oral bioavailability of poorly water-soluble drugs in a simple and cost-effective manner.

FORMULATION AND INVITRO EVALUATION OF SOLID DISPERSION TABLETS OF SILYMARIN

Objective: The research aims to formulate and evaluate Solid Dispersion tablets of Silymarin. Methods: Solid dispersions of Silymarin were prepared with various concentrations of carriers by using solvent evaporation method. The prepared solid dispersions were compressed into tablets by using 8 mm punch rotary tablet punching machine, with the hardness of 3.5kg /cm2.The formulated tablets were evaluated for various quality control parameters. Results: Silymarin was mixed with various proportions of excipients which showed no drug-excipients interactions. The precompression blend of Silymarin solid dispersions were characterized with respect to angle of repose, bulk density, tapped density, Carrs index and Hausners ratio. The precompression blend of all the batches indicated good to fair flowability and compressibility. Conclusion: The tablet passed all the tests. Among all the formulations F4 formulation containing, Drug and PEG 4000 in the ratio of 1:4 showed good result that is 94.95 % in 60 minutes. As the concentration of polymer increased the drug release was increased. While the formulations containing PEG 6000 showed less release. Hence from the dissolution data it was evident that F4 formulation is the better formulation.

Formulation and Evaluation of Obeticholic Acid Solid Dispersion Tablet

Obeticholic acid is a farnoside X receptor agonist that was recently licenced by the US Food and Drug Administration. In a solvent, solubility is lower, therefore it is necessary to improve solubility. Solid dispersion is one of the most effective methods for increasing Obeticholic acid's solubility. Solid dispersion can be prepared in a variety of ways. Fusion (Hot Melting) is one of the most straightforward and cost-effective methods for producing solid dispersion. Poloxamer is one of the finest polymers for solid dispersion production. Poloxamer 188 and Poloxamer 407 are widely accessible. Above solid dispersion is made using the fusion or hot melting procedure. The solubility of the prepared solid dispersion has increased to 0.347 mg/ml. In comparison to the polymer combination, which has a drug release rate of 99.63 percent, the percent drug release is also superior. Precompression settings were found to be within a reasonable range. Post compression parameters such as Hardness, Friability, Uniformity of weight, content uniformity are in standard range. F7 formulation shows 99.63 ± 0.19 in 60 minutes of time. Phosphate buffer 7.4 is used for dissolution test apparatus. All result parameter shows that prepared solid dispersion of Obeticholic acid by using poloxamer gives improved solubility and increased drug release.