Hydrochloride Tablets Research Articles

Pharmacokinetics and Bioequivalence of Vardenafil Hydrochloride in Healthy Chinese Volunteers.

Vardenafil hydrochloride tablet is an inhibitor of phosphodiesterase type 5, primarily for the treatment of erectile dysfunction. This postprandial study evaluated the pharmacokinetics and bioequivalence of the test and reference formulations of vardenafil hydrochloride tablets in healthy Chinese volunteers. An open, randomized, single-center, single-dose, 2-period, 2-sequence bioequivalence test was conducted on 66 healthy subjects under fed conditions. Subjects were randomly assigned to a 20-mg test or reference formulation with a 7-day washout period. Venous blood samples (4mL) were collected from each subject 25 times spanning predose (0hour) to 24hours after dosing. The plasma concentration of vardenafil was determined by high-performance liquid chromatography-tandem mass spectrometry. Sixty-two volunteers completed the study. Under fed conditions, the maximum plasma concentration was 29.1ng/mL, the area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration was 85.3ng•h/mL, and AUC from time 0 to infinity was 87.1ng•h/mL. The 90% confidence intervals of the geometric mean ratio of AUC time 0 to the time of the last measurable concentration and AUC from time 0 to infinity were within the bioequivalence acceptance range of 0.80-1.25. The test formulation was a bioequivalent alternative to the reference formulation when taken under fed conditions in healthy Chinese subjects.

Retrospective Study on the Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation Combined with Tiapride Hydrochloride Tablets in Children with Attention Deficit Hyperactivity Disorder.

This study aimed to explore the application effect of repetitive transcranial magnetic stimulation (rTMS) combined with tiapride hydrochloride tablets in children with attention deficit hyperactivity disorder (ADHD). The medical records of 197 children with ADHD in our hospital from January 2022 to January 2023 were retrospectively analysed. Seven children who did not meet the inclusion criteria were excluded, and 190 children were finally included in this retrospective study. Based on the different clinical therapeutic methods, these children were divided into tiapride (n = 64), rTMS (n = 64), and combination (n = 62) groups. The clinical effects of different therapeutic schemes were compared. The clinical effectiveness and the scores of Swanson, Nolan, and Pelham Rating Scale Version IV (SNAP-IV), Conners Parent Symptom Questionnaire (PSQ), and Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) were compared among the 3 groups. There was no significant difference in gender, age, course of disease, weight, and WISC-IV score among the combination, tiapride, and rTMS groups (all P > .05). The effective rate of treatment in the combination group (93.55%) was significantly higher than that in the tiapride group (78.13%) and the rTMS group (81.25%). There was a significant difference in the comparison of the combination group with the tiapride group (P = .013) and the rTMS group (P = .038). Before treatment, no significant difference existed in the scores of attention deficit symptoms and hyperactivity disorder symptoms among the 3 groups (all P > .05). After 3 months of treatment, the difference score of the combination group before and after treatment was significantly higher than that of other 2 groups (all P < .001). Before treatment, no significant difference was found in the scores of conduct problems, learning problems, psychosomatic disorders, impulsive hyperactivity, anxiety and hyperactivity index among the 3 groups (all P > .05). After treatment, the combination group had significantly higher difference score before and after treatment than other 2 groups (all P < .001). There was no significant difference in WFIRS-P scores among the 3 groups before treatment (all P > .05). After treatment, the difference score in the combination group before and after treatment was significantly higher compared with other 2 groups (all P < .001). Transcranial magnetic stimulation combined with tiapride hydrochloride tablets had a positive effect on improving the condition of children with ADHD, with certain clinical promotion value.

A novel, green and affordable semi-quantitative limit test for 2-aminobutanol impurity in ethambutol hydrochloride bulk and tablets

The pharmacopoeial limit test for the impurity 2-aminobutanol (AB) in ethambutol hydrochloride (ETB) relies on florescence measurement using a fluorometer. However, this instrument is often unavailable in many laboratories due to its cost. A novel colorimetric method was therefore developed using genipin, an amine-reactive reagent, to react with AB, producing a blue color. The color intensity was subsequently measured using a more affordable UV-vis spectrophotometer. To overcome matrix effects, the standard addition technique was incorporated. The test effectively detected AB at concentrations as low as 0.125% in ETB, below the compendial limit of 1.0%. The analysis of ETB bulk and tablets showed consistent semi-quantitative results with the USP method. Furthermore, it aligned with green chemistry by eliminating the use of organic solvents and employing safe, naturally derived reagent. In summary, the proposed method provides a reliable, green, and cost-effective alternative for analyzing AB in ETB, ensuring compliance with pharmacopeial standards.

Specific surface area of mannitol rather than particle size dominant the dissolution rate of poorly water-soluble drug tablets: A study of binary mixture

The dissolution behavior of tablets, particularly those containing poorly water-soluble drugs, is a critical factor in determining their absorption and therapeutic efficacy. Traditionally, the particle size of excipients has been considered a key property affecting tablet dissolution. However, lurasidone hydrochloride (LH) tablets prepared by similar particle size mannitol, namely M200 (D90 = 209.68 ± 1.42 μm) and 160C (D90 = 195.38 ± 6.87 μm), exhibiting significant differences in their dissolution behavior. In order to find the fundamental influential factors of mannitol influencing the dissolution of LH tablets, the properties (particle size, water content, true density, bulk density, tapped density, specific surface area, circularity, surface free energy, mechanical properties and flowability) of five grades mannitol including M200 and 160C were investigated. Principal component analysis (PCA) was used to establish a relationship between mannitol properties and the dissolution behavior of LH. The results demonstrated that specific surface area (SSA) emerged as the key property influencing the dissolution of LH tablets. Moreover, our investigation based on the percolation theory provided further insights that the SSA of mannitol influences the probability of LH-LH bonding and LH infinite cluster formation, resulting in the different percolation threshold states, then led to different dissolution behaviors. Importantly, it is worth noting that these findings do not invalidate previous conclusions, as reducing particle size generally increases SSA, thereby affecting the percolation threshold and dissolution behavior of LH. Instead, this study provides a deeper understanding of the underlying role played by excipient SSA in the dissolution of drug tablets. This study provides valuable guidance for the development of novel excipients aimed at improving drug dissolution functionality.

Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.

Utilization of absorbance subtraction and ratio difference green spectrophotometric methods for the quantification of alfuzosin hydrochloride and tadalafil in their binary mixture

Alfuzosin hydrochloride and tadalafil fixed-dose combination tablets were recently formulated for the treatment of individuals with lower urinary tract symptoms caused by benign prostatic hyperplasia. Herein, the first spectrophotometric methods for quantitative analysis of alfuzosin hydrochloride and tadalafil in their binary mixture were established. The spectral overlapping of alfuzosin hydrochloride and tadalafil made direct simultaneous analysis unfeasible. Therefore, two mathematical methods were used to solve these overlapping spectra: absorbance subtraction and ratio difference. The absorbance subtraction method manipulates the zero absorption spectra of the studied drugs at the isoabsorptive point (272 nm) and uses the absorbance factor of pure ALF to calculate the absorbance of the studied drugs in the mixture at the isoabsorptive point. The ratio spectra method, on the other hand, manipulates the ratio spectra of the studied drugs, which are obtained by dividing each drug’s zero absorption spectra by a divisor spectrum from the second drug. The ratio amplitude difference between 251 nm and 211 nm was directly proportional to alfuzosin hydrochloride, whereas between 292 nm and 222 nm it was directly proportional to tadalafil. The methods used were verified in accordance with the recommendations of the ICH and demonstrated adequate linear regression in working ranges of 1–15 µg/mL for alfuzosin hydrochloride and 3–40 µg/mL for tadalafil. The methods were accurate, precise, and selectively employed to quantify alfuzosin hydrochloride and tadalafil in their combined tablets.

Exploring The Differences : A Comparative Analysis of Pharmaceutical Quality of Different Brands of Metformin Hydrochloride Tablets

Type 2 diabetic patients can regulate their increased blood sugar levels using metformin, an antidiabetic medicine approved by the FDA. It decreases the quantity of glucose produced by the liver, lessens the glucose absorption from the intestines, and raises insulin sensitivity. For best effects, metformin should be used in conjunction with dietary modifications and physical activity. The first-line oral hypoglycemic medication for type 2 DM(Diabetes Mellitus) is thought to be metformin. The recommended medication for obese people is MET. AMPK- Adenosine monophosphate-activated protein kinase, a liver enzyme crucial to insulin signaling, is triggered by metformin. Metformin’s inhibitory effect on hepatic cell glucose synthesis necessitates AMPK activation. This study aims to compare the pharmaceutical quality of three different brands of metformin hydrochloride tablets. All the three brands were evaluated for uniformity of weight, friability, hardness, dissolution, disintegration and assay was performed. All the brands tested were within the specification, thus all the tablets passed the pharmaceutical quality test, however, variations exist between brands, which could be due to differences in excipients, pressure during compression, manufacturing procedure etc.

Formulation, characterization and evaluation of vildagliptin and metformin combined tablets

The current study was conducted to formulate and assess combined vildagliptin (VD) and metformin hydrochloride (MET) tablets. The formulations were developed by wet granulation to overwhelm the reduced compressibility of MET powder. Polymers like Kollidon K30 and K90 were used to prepare formulations. Micromeritics characteristics of blends were assessed. Subsequently, the tablets that had been manufactured were assessed for post-compression characteristics. The composition formula F7 was optimal due to having the best hardness, friability and good dissolution.

FORMULATION AND EVALUATION OF CLINDAMYCIN HYDROCHLORIDE FLOATING DRUG DELIVERY

The Clindamycin Hydrochloride is a broad spectrum cephalosporin antibiotic. It is mainly used to treatment of bacterial infections. It is a suitable candidate for controlled release administration due to its short elimination time 1 hours. The main aim of present investigation is to increase the gastric residence time by preparing floating drug delivery by using raft forming approach thereby improving bioavailability. The prepared Clindamycin Hydrochloride floating drug delivery were evaluated for hardness, weight variation, thickness, friability, drug content uniformity, total floating time, In-vitro dissolution studies and buoyancy lag time. Floating tablets were formulated using direct compression technique. Various polymers are used in the formulation they Micro crystalline cellulose used as binder, HPMC K15M, Guargum used as hydrophilic polymers, Chitosan, Sodium bicarbonate was incorporated as an effervescent substance, Sodium alginate used as viscous gel forming agent, Magnesium streate used as lubrication, talc was used as diluent. The formulated Clindamycin Hydrochloride tablet to be evaluated the following parameters as follow Weight variation (mg), Hardness, Thickness, Friability, Drug content uniformity, Floating lag time, the in vitro cumulative amount of drug released was shown the F4 is 99% within 12 Hours the comparative studies with marketed formulations F4 show the better results. In vitro release rate studies showed that the maximum drug release was observed F4 formulation up to 12 hours. KEYWORDS: Clindamycin Hydrochloride, Direct compression, Floating drug delivery system.

Comparative evaluation of some moxifloxacin hydrochloride tablet brands marketed in Nigeria using five different validated analytical methods

Background: Assay of pharmaceuticals is an important aspect of quality control. It is necessary to compare the bioequivalence of generic brands of the any drug to an innovator/comparator brand as this forms the basis for comparing their therapeutic equivalence.Objective: This study aimed to determine the most accurate method for the assay of moxifloxacin hydrochloride (MOX-HCl) tablet brands in Nigerian markets by using five different validated analytical methods and also verify their interchangeability.Material &amp; Methods: This study involved three brands of MOX-HCl including the comparator brand, Moxiget®. The study involves both quality control tests including: weight uniformity, diameter, thickness, friability, hardness, disintegration, dissolution and content of active ingredient (assay) methods including: phosphate buffered UV-Vis spectrophotometric, UV spectrophotometric, kinetic spectrophotometric, colorimetry and utilization of oxidation-reduction reaction methods.Results: All the samples used for this study passed the quality control tests and thus were of standard quality and therefore pharmaceutically equivalent.Conclusion: This study therefore conclude that phosphate buffered UV-Vis spectrophotometry provide the most accurate method to assay Moxifloxacin tablet, colorimetry assay method can serve as a substitute to the preferred method for the moxifloxacin assay and the three samples assayed in this work are interchangeable with the comparator brand (Moxiget®).

Quality assessment of metformin hydrochloride tablets retailed in Lagos, Nigeria

Background: Metformin is a biguanide antihyperglycemic drug used with diet and exercise for glycemic control in type 2 diabetes mellitus.Objectives: This research aims to compare and analyze different metformin products to ascertain their critical quality parameters. The goal is to ensure that prescribed medicine effectively treats patients and protects the public.Materials and Methods: We evaluated the quality of ten metformin tablet brands in Lagos (Mushin and Surulere area) using official methods to assess weight, hardness, friability, disintegration time, and dissolution. Active ingredient content was also measured.Results: Out of all the tablets tested, only 10 % had weights outside of the official British Pharmacopoeia 2002 limits (not more than two tablets should deviate from ±5% and none of the tablets should deviate by ± I0). The hardness test was passed by all the tablets (A minimum hardness of 4 kgF is a pass), while 80 % passed the friability test (weight loss of ≤ 1 %w/w is a pass). Additionally, all film-coated tablets disintegrated within 30 minutes according to United States Pharmacopoeia/National Formulary 2003 (film-coated tablets disintegrate within 30 minutes). Ninety percent of the tablets passed the dissolution test (drug release within 60 minutes should be between 93 and 103 %) and 90 % of all brands examined passed the assay test for the active ingredient contents. The British Pharmacopoeia 2019 standard was used for the dissolution test.Conclusion: Routine pharmaceutical analysis is essential for the quality of pharmaceutical products and the safety of consumers.

Age-related pharmacokinetics differences were observed between young and elderly populations of a novel PDE5 inhibitor, youkenafil, and its metabolite M459

PurposeYoukenafil is a novel oral selective PDE5 inhibitor for treating Erectile Dysfunction. This investigation assessed pharmacokinetics (PK), safety, and tolerability of youkenafil and its main metabolite (M459) after taking 100 mg youkenafil hydrochloride tablets in elderly and young subjects. MethodsThis Phase I, single-center, open-label, parallel-group, single-dose study was conducted on 24 individuals (12 elders and 12 youngsters). Each subject received a single oral 100 mg youkenafil hydrochloride tablets. Blood samples were collected before medication and up to 48 h after medication for PK analysis. Safety and tolerability were also assessed, including treatment-emergent adverse events (TEAEs), laboratory tests, 12-lead ECG, vital sign inspections, color vision examinations, and physical examinations. ResultsPlasma concentrations of youkenafil and M459 were quantified. PK parameters were determined by non-compartmental analysis. Median Tmax of elderly and young groups were both 0.733 h. However, Cmax, AUC0-t, and AUC0-∞ of youkenafil were separately 16.8 %, 37.2 %, and 37.5 % higher in elders and t1/2 of youkenafil was 2.1 h longer in elders. More great differences were observed for M459. T1/2 values were 4.05 h longer in elders, with Cmax, AUC0-t and AUC0-∞ 73.7 %, 81.1 %, and 81.4 % higher in elders. Two (8.3 %) elderly subjects reported TEAEs (all grade Ⅰ in severity) and both recovered without any treatment. No serious adverse reactions (SAEs) or serious unexpected suspected adverse reactions (SUSARs) occurred in this study. ConclusionsThis was the first PK research of youkenafil and M459 in elderly men. PK parameters differences between youkenafil and M459 were comparable between elderly and young groups. Moreover, safety and tolerability of youkenafil were favorable in both groups.

DEVELOPMENT AND EVALUATION OF METFORMIN TABLETS: EFFECT OF SUPERDISINTEGRANTS

Metformin is an oral antihyperglycemic medication used to treat type 2 diabetes. BCS-III classification of medications includes metformin hydrochloride, which has a high solubility and a low permeability. This study’s objective was to develop wet granulated metformin hydrochloride tablets using various synthetic superdisintegrants. On disintegration and dissolution, the effects of different superdisintegrants have been studied. After evaluation, it were observed that post-compression properties such as weight variability, thickness, hardness, and friability were within the IP ranges. The formulation F4 with Croscarmellose sodium (CCS) in low concentration was chosen as the best formulation. By increasing the quantity of Croscarmellose sodium (CCS), the in vitro dissolution profile increased, and in vitro disintegration time also increased in the formulated tablets using wet granulation method. The statistical significance was determined using one-way ANOVA, and there is no significant difference between formulations.

Development and Evaluation of Venlafaxine Hydrochloride Tablets for Oral Drug Delivery Technology

Oral pills are the predominant, simple, and straightforward approach for administering drugs. The project’s primary goal is to create a pharmaceutical product that is equal in terms of its medicinal properties. A controlled-release version of the antidepressant venlafaxine hydrochloride was created and compared to the formulation currently available on the market. The launch of the branded product was assessed through an innovator and prototype evaluation. In order to develop stable and bioavailable dosage forms, it is necessary to gather pertinent data through preformulation testing. In order to create stable and bioavailable dosage forms, preformulation testing must be performed to gather relevant information among the several mixes, high-performance polymer copolymer K100M, ethyl cellulose, and cross-linked polyvinyl pyrrolidone 0.45%. The precise release mechanism could be determined by conducting in-vitro solubility tests on the created formulations and analyzing the results with a number of exponential equations. We used fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) studies to check if the polymers were compatible with the medicine.

Development and Evaluation of Trazodone Hydrochloride Tablets for Oral Drug Delivery Technology

Development and Evaluation of Trazodone Hydrochloride Tablets for Oral Drug Delivery Technology

The feasibility of Raman spectroscopy for accurate assessment of essential criteria in pharmaceutical industry by investigation of Metformin hydrochloride tableting process

AbstractAnalytical and real‐time technology in pharmaceutical manufacturing process is an important need to ensure that manufactured drugs are safe and effective. Raman spectroscopy is an emerging technique that is able to perform quantitative analysis nondestructively due to the molecular structure of many drugs. Monitoring the content uniformity and quantification of active pharmaceutical ingredient (API) in the tablet preparation process, without the assistance of solvent, is one of the key concerns in the formulation design in order to provide stable, pure, and homogenous finished products. In this study, we investigated the possibility of using Raman data as an analytical method to quantify API, the intra‐ and inter‐sample uniformity of content in the tableting process of Metformin hydrochloride tablets (C4H11N5.HCl). Analysis of all standard samples for prediction of API uniformity represents an acceptable accuracy and precision with a relative standard deviation of 2.55%. Further investigation of tablets regarding to relative Raman intensity of some characteristic peaks demonstrates the amount of API content with an accuracy of ≥96%. These values have a good adaption with pharmacopeia monograph. Findings reveal that the Raman method can be routinely utilized for quantifying API, controlling the content uniformity and the stability of drugs in different stages of manufacturing.

Bioequivalence Assessment of Two Dapoxetine Hydrochloride Formulations in Healthy Chinese Males Under Fasted and Fed Conditions.

This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single-center, 2-period, 2-sequence, randomized, open-label, self-crossover study with a washout period of 14 days, 30 in the fasted group and 30 in the fed group. Following a single 30-mg oral dose of the test or reference dapoxetine formulation, blood samples were collected before dosing to 72 hours after dosing. Liquid chromatography-tandem mass spectrometry was performed to measure plasma concentration of dapoxetine and determine pharmacokinetic parameters through noncompartmental analysis. The vital signs and adverse events were also monitored during the study. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last concentration time, and area under the plasma concentration-time curve from time 0 extrapolated to infinity of the 2 dapoxetine formulations completely fell within the regulatory criteria for bioequivalence of 80%-125%. In addition, both dapoxetine hydrochloride formulations were generally well tolerated. The generic dapoxetine hydrochloride tablet was bioequivalent to the marketed reference product in healthy Chinese men with no discernible safety differences.

Assessing Abuse-Deterrent formulations utilizing Ion-Exchange resin complexation processed via Twin-Screw granulation for improved safety and effectiveness

Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist–antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.

Evaluation of Seven Different Brands of Metformin Hydrochloride Tablets Available in the Market in Gondar City, Ethiopia.

WHO estimates that 15.8% of substandard or falsified medical products are used to treat non-communicable diseases which account for 80% of the global burden including diabetes. The increased level of use of metformin hydrochloride tablets in clinical practice creates the need to monitor and ascertain the quality of the various brands available in the drug market for quality control assessment and generic substitution. This study aims to assess the pharmaceutical quality of seven brands of metformin tablets circulating in pharmacy outlets in Gondar City, North West Ethiopia. Official Pharmacopoeia tests such as uniformity of weight, disintegration, assay, and dissolution tests were used to assess the physicochemical quality control parameters of metformin hydrochloride tablet brands. The unofficial tests conducted included crushing strength/hardness and friability. In all seven tests, the tested brands passed the BP official tests for uniformity of weight, friability, disintegration, and dissolution. Each product had a friability of less than 1% with a maximum of 0.385%. In contrast, none of the brands passed the non-official hardness test. Each product disintegrated in seven to twelve minutes, meeting the USP standards. Drug release rates in 45 min ranged from 78.9 to 92.6%, and drug content results were within the USP guidelines (96.55-102.76%). The current study demonstrated that all seven brands of metformin hydrochloride 500 mg tablets adhered to the quality control parameters specified in the pharmacopeia, except for the hardness test across all brands.

In vitro release and bioaccessibility of oral solid preparations in a dynamic gastrointestinal system simulating fasted and fed states: A case study of metformin hydrochloride tablets

Food and formulation characteristics are crucial factors affecting the gastrointestinal release and absorption kinetics of oral solid preparations. In the present study, the dynamic continuous release and bioaccessibility of metformin hydrochloride immediate-release (IR) and sustained-release (SR) tablets were investigated in the dynamic human stomach-intestine (DHSI-IV) system simulating fasted and fed states in healthy adults. Both tablet formulations (particularly IR tablet) exhibited a postponed release in the fed state compared to the fasted state. Correspondingly, the bioaccessible fraction of metformin from IR tablets in the presence of high-fat meal was significantly reduced to 76.2 % of the fasted state. However, the in vitro bioaccessibility was less impaired by food for SR tablets with a fed/fasted ratio of 95.5 %. A convolution-based approach was used to convert in vitro bioaccessibility results to plasma concentration data. The predicted plasma concentration curve showed good agreement with human data in terms of pharmacokinetic (PK) parameters. In the fasted state, the predicted Cmax, Tmax and AUC0-24h of IR tablets were 943.9 ± 25.7 ng/mL, 2.0 ± 0.4 h and 7090.7 ± 112.0 ng.h/mL, respectively, mirroring values observed in healthy subjects. Overall, the DHSI-IV system has demonstrated potential to assess and predict the impact of meal intake on the in vivo release and absorption behaviors of oral solid preparations.