Controlled-release Tablets Research Articles

Analysis of Efficacy of Valsartan Combined with Nifedipine Controlled-release Tablets in the Treatment of Hypertension in Community

Analysis of Efficacy of Valsartan Combined with Nifedipine Controlled-release Tablets in the Treatment of Hypertension in Community

An Integrative QbD Approach for the Development and Optimization of Controlled Release Compressed Coated Formulation of Water-Soluble Drugs

Controlled release dosage forms maintain regulated pharmacokinetic profile of drug substance within its therapeutic window by ensuring constant plasma concentrations. Controlled release formulations not only increase the therapeutic efficacy of drug substances but also reduce their dose-related side effects. Present investigation was conducted to develop, optimize, and validate compressed coated controlled release tablet formulation for highly water-soluble drug substances which have no rate-controlling factor towards its release from dosage form. Drug dispersed waxy core tablet, press coated within the swellable hydrophilic polymeric barrier layer, was developed and optimized via quality by design approach (QbD) using Box-Behnken design. The optimized formulation was characterized and validated using in vitro quality control parameters. Attributes identified under SUPAC guidelines, such as drug release rates at 30 min, 6 h, and 12 h, were considered as the critical quality attributes (CQAs) that significantly affected efficiency of the compressed coated controlled release tablets. CQAs screened using risk assessment and Pareto chart analyses were used for optimizing controlled release dosage form. Findings revealed that tablets containing drug to wax ratio of 1:1, hydrophilic swellable polymer concentration of 200 mg, and prepared using compression pressure of 6.5 kg/cm2 exhibited the highest desirability indices in terms of controlling the release rate of drug substance. Optimized formulation was also evaluated for swelling rate, erosion rate, and other post-compression parameters, including release kinetics. Fickian diffusion-based zero-order controlled release of BCS class I drug substance was achieved through the developed dosage form.

Development and validation of HPLC-DAD and LC-(ESI)/MS methods for the determination of sulfasalazine, mesalazine and hydrocortisone 21-acetate in tablets and rectal suppositories: In vitro and ex vivo permeability studies

Controlled-release tablets and rectal suppositories of sulfasalazine (SLF) and hydrocortisone 21-acetate (HA) were prepared as recommended dosage forms for the treatment of acute episodes of ulcerative colitis, in patients who do not respond to monotherapy.A High-Performance Liquid Chromatography (HPLC) Diode-array method with a gradient elution mobile phase was developed to evaluate the production quality of both formulations (assay and dissolution profiles in gastric and intestinal fluids). Method's validation was carried out providing good linearity (r ≥ 0.9995), precision (RSD < 1.53%), recovery (96.9% − 103.7%) and limits of detection (LODSLF = 12 ng/mL, LODHA = 15 ng/mL). Experimental design and Plackett-Burman methodology was constructed to study the robustness of the analysis. In all composite substrates, a freezing lipid precipitation approach was used as purification step. The method was optimized by applying Central Composite design mode.The in-vitro/ex-vivo permeability studies of both formulations were evaluated by a Liquid Chromatography-Electron Spray Ionization Mass Spectrometry (LC-ESI/MS) +/- mode. The analysis of sulfamethazine (internal standard, SLM, m/z 279), HA (m/z 449, [M + HCOO]-), SLF (m/z 399) and its active metabolite mesalazine (MSL, m/z 154) was performed using a C18 column and gradient elution. The validation of the method met the requirements of the International Council for Harmonization (ICH) (r ≥ 0.9997, RSD ≤ 4.62%, Recovery > 95%, LODSLF = 1.28 ng/mL, LODHA = 1.07 ng/mL, LODMSL = 3.16 ng/mL). Based on the results, important conclusions were drawn concerning the role of excipients and SLF metabolism.

Efficacy and Safety of SID142 in Patients With Peripheral Arterial Disease: A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group, Phase III Clinical Trial

Renexin® is a combination pill of cilostazol and Ginkgo biloba leaf extract that is used for the improvement of ischemic symptoms associated with peripheral arterial disease (PAD). SID142 is a controlled-release tablet of cilostazol (200 mg) and G biloba leaf extract (160 mg) that was developed to address the limitation of BID administration with Renexin. This study aimed to verify that SID142 was not inferior to Renexin in the treatment of patients with PAD. This was a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase III clinical trial. Study subjects were randomized to receive SID142 once daily or Renexin twice a day for 12 weeks. The primary end point was a change in the patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. If the lower limit of the two-sided 95% CI was greater than -10, the study drug was declared noninferior to the reference drug. Secondary efficacy end points included cold sensation, ankle-brachial index, ankle systolic pressure, maximum walking distance, pain-free walking distance, and investigator's global assessment. Study group results were compared 4, 8, and 12 weeks after treatment. Adverse events were assessed as a safety end point. In total, 344 subjects from 19 medical centers were screened, and a total of 170 subjects were randomly assigned to either the SID142 (n=86) or the Renexin (n=84) group. Analysis of the change in lower extremity pain at 12 weeks compared with baseline revealed that SID142 was not inferior to Renexin (21.44 [19.23] vs 22.30 [17.75]; 95% CI, -7.70 to 5.97; P=0.5942). No significant differences were found between groups in any secondary efficacy end point. However, the incidence of adverse reactions was significantly lower in the SID142 group (22.35% vs 39.29%; P=0.0171). SID142 once daily was not inferior to Renexin twice a day for efficacy in patients with PAD. SID142 had a favorable safety profile. gov identifier: NCT03318276.

Rheological Investigation of Hydroxypropyl Cellulose-Based Filaments for Material Extrusion 3D Printing.

The rheological properties of drug–polymer mixtures have a significant influence on their processability when using transformative techniques, such as hot-melt-extrusion and material-extrusion 3D printing; however, there has been limited data on printable systems. This study investigated the rheological properties of 17 formulations of successful printed tablets for both immediate and controlled release. Hydroxypropyl cellulose was used in various ratios to obtain printable filaments in combination with various drugs (indomethacin or theophylline), polymers and disintegrants. The complex viscosity, shear thinning behavior and viscoelastic properties were affected by the drug load, polymer composite, disintegrant type, temperature and shear rate applied. Larger windows of processing viscosity were revealed. The viscosity of the printable blends could be as low as the range 10–1000 Pa·s at 100 rad/s angular frequency. All formulations showed shear thinning behavior with a broad slope of complex viscosity from −0.28 to −0.74. The addition of 30–60% drug or disintegrant tended to have greater viscosity values. While microcrystalline cellulose was found to be an alternative additive to lower the storage and loss modulus among disintegrants. This rheological data could be useful for the preformulation and further development of material-extrusion 3D-printing medicines.

Preparation and in Vitro Evaluation of Osmotic-Pump Lorcaserin-hydrochloride Controlled-Release Tablets.

Long-term and constant-release osmotic-pump lorcaserin hydrochloride controlled-release tablets (OP LH CRTs) were prepared, to investigate the influencing factors of LH release and optimize the formulation. The mechanism of release of LH from OP LH CRTs in vitro was investigated. By establishing a high-efficiency method for measuring LH release in vitro, and optimizing it by single-factor and orthogonal experiments, the best formulation of OP LH CRTs was determined. Then, the optimal prescription of OP LH CRTs was: LH = 20.8 mg; mannitol = 100 mg, microcrystalline cellulose = 125 mg; magnesium stearate = 5 mg; cellulose acetate = 3%; polyethylene glycol 400 = 10%; dibutyl phthalate = 10%; Wetting agent and binder was 3% polyvinyl pyrrolidone (PVP) K30 ethanol solution; aperture diameter = 0.8 mm; the coating gained 3% weight. And finally, prepared OP LH CRTs were released at a constant rate in vitro and sustained for 16 h with good reproducibility between batches. Using an orthogonal experimental design, OP LH CRTs with remarkable zero-order release characteristics within 16 h were obtained, and formulation optimization was realized.

Plus ça change? Switching lithium preparations.

A supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel® (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective. Data on the treatment of 37 patients switched from Priadel® tablets were analysed. Switching to Camcolit® controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands. For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex.

Formulation and Evaluation of Cilnidipine Solid Dispersions and Oral Controlled Release Tablets

Drug solubility plays an important role in the improvement of bioavailability. Biopharmaceutical Classification System (BCS) Class-II drugs have less solubility and more permeability. Most of the drugs available in the market belong to BCS class-II. The objective of the present study is to improve the solubility of BCS Class-II drug, Cilnidipine by formulating them as solid dispersions and to make controlled release formulations. Solid dispersions of Cilnidipine were prepared by solvent evaporation technique using plasdone K29/32. Various physical parameters were evaluated for the prepared solid dispersions. The in vitro drug release studies were performed for the solid dispersions using phosphate buffer pH 6.8. The solid dispersions which showed maximum drug release were selected for the preparation of oral controlled release formulations. Tablets were prepared using Cilnidipine solid dispersions and varying concentrations of polyethylene oxide (PEO) WSR 303 by direct compression technique. Pre and post-compression parameters were evaluated along with in vitro drug release studies. In vitro dissolution studies revealed that solid dispersion CP3 containing Cilnidipine and plasdone K29/32 in 1:3 ratios showed faster drug release in a short time. The pre and post compression parameters of the solid dispersions and tablets were within specified limits. Formulation CPP5 containing CP3 solid dispersion with 25% w/w of PEO WSR 303 showed prolonged drug release up to 12h. Similar drug release was also obtained with CPP6 formulation having 30%w/w of PEO WSR 303. The present study prepared a novel Cilnidipine pharmaceutical product having increased solubility and prolonged drug release which is not available in the market. The solubility of Cilnidipine was enhanced using plasdone K-29/32 and the drug release was delayed using PEO WSR 303 as polymer. This could be advantageous to many of the patients with cardiovascular disorders

Optimization and Quest of HPMC loaded Stavudine Controlled Release Dosage Development by Central Composite Design utilizing Reduced Factorial Screening Technique

The current research focused on screening and finding the significant independent variables in stavudine loaded tablet, followed by optimizing the best formulation using central composite design. The objective of the study to develop stavudine loaded controlled release tablet utilizing reduced factorial design, followed by optimization technique as well as characterization of prepared tablets. Preliminary trial batches were prepared using different grades of hydroxypropyl methylcellulose. The resolution-IV reduced factorial design was selected to screen the significant independent variables in the dosage form design. A total number of eight runs were prepared and responses were recorded. The signified factors identified by half-normal and Pareto chart. The prepared tablets are evaluated for various physiochemical characterizations. Three dependent responses such as hardness, dissolution at 6 hour and 12 hours are considered in optimization process. Later on, drug-polymer interaction study was carried out. The principal of the study design based on finding the best formulation with prefixed set parameter values utilizing the concept of screening technique. It observed that HPMC K15M (57.18 %), HPMC K100 (66.32 %) and PVP K30 (7.97 %) as best composition in a formulation batch would fulfill the predetermined parameter with specific values.

Development of Novel Etodolac Matrix Tablet and their Pharmaceutical Characterization

The current work poses a difficulty in producing etodolac oral controlled release tablets using five of the most well-known hydrophilic release rate retardant polymers, including non-toxic materials like HPMC K4M, Carbopol 974, and Eudragit RS100. The batches were created using the wet granulation process. According to the prescribed methods, the pre-and post-compression properties were evaluated. To identify the likely drug release mechanism, the formulations were tested for their capacity to release the drug in the simulated gastric medium. The results were then fitted into several kinetic model(s). The investigation of short-term stability was also carried out. The bulk and tapped densities, which are in the range of 0.85 to 0.86 g/cm3 and 0.95 to 0.98 g/cm3, respectively, show an excellent pre-compression feature. The drug concentration was discovered to be between 98.26%-100.15%. The formulation F3 (102.95%) had the maximum in vitro drug release because it had the ideal concentration of polymer combination, which delayed the drug release and used the diffusion cum erosion process (s). When matrix formulations are carefully fabricated, the frequency of medication administration may be reduced to twice daily while also reducing blood level variations, which ultimately improves patient compliance and therapy regimens.

Analysis of the improvement of serological indexes in patients with diabetic nephropathy and hypertension using Valsartan combined with Nifedipine controlled-release regimen.

Objective:To investigate the effect of valsartan combined with nifedipine controlled-release Tablets on diabetic nephropathy (DN) patients with hypertension.Methods:The clinical records of 80 DN patients with hypertension registered in our hospital from April 2020 to April 2021 were collected. The records showed that 38 patients were treated with oral nifedipine controlled-release tablets (control group) and 42 - with oral valsartan combined with nifedipine controlled-release tablets (observation group). The improvement of serological indexes after treatment was compared and analyzed between the two groups.Results:After treatment, the levels of fasting blood glucose (FBG), systolic and diastolic blood pressure, bone oligomeric matrix protein (COMP), thrombin regulatory protein (TM) and Microalbumin (mALB) in the observation group were lower than those in the control group (P<0.05), while the level of angiopoietin-1 (Ang-1) was higher than those in the control group (P<0.05). After the treatment, the levels of homocysteine (Hcy), Cystatin C (CysC) and transforming growth factor β1(TGF-β1) in the observation group were lower than those in the control group (P<0.05). The levels of adiponectin (APN), aldosterone (ALD) and gastric growth promoting factor (ghrelin) in the observation group after the treatment were lower than those in the control group (P<0.05).Conclusions:A combination of valsartan and nifedipine controlled-release tablets in DN patients with hypertension can effectively control blood glucose and blood pressure, improve the serological indexes such as COMP, TM, mAlb, Ang-1, Hcy, CysC, TGF-β1, APN, ALD and ghrelin, and potentially reduce and delay renal function damage.

A Model to Predict Drug Release from a Single-Layer Osmotic Controlled-Release Tablet

A Model to Predict Drug Release from a Single-Layer Osmotic Controlled-Release Tablet

Development and Evaluation of Controlled Release Formulations of Esomeprazole

The present work was aimed to development of controlled release formulations of Esomeprazole to improve bioavailability. Esomeprazole is the proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity. Construction of calibration curve of Esomeprazole and to investigate the drug and polymer interaction studies by FTIR and DSC. To prepare the different controlled release formulations of Esomeprazole tablets with different polymers like Polymethacrylates such as Eudragit-S100, Eudragit-L100, Eudragit-RSPO, Eudragit-RS100, Eudragit-RL100 and Eudragit RLPO by Direct Compression method. Evaluation of Esomeprazole pre compression parameters such as Bulk density, Tapped density, Hausner’s ratio, Carr’s index, Angle of repose. Evaluation of post-compression parameters of Esomeprazole controlled release tablets such as Weight variation, Hardness, Friability test, Thickness, Drug Content and In-vitro dissolution studies. Evaluation of in-vitro dissolution uniqueness of all the formulations of Esomeprazole by using USP dissolution apparatus type-II (paddle). To study the mechanism of drug dissolution by applying kinetic parameters. To perform the stability studies of optimized formulations of Esomeprazole as per ICH guidelines.

Urinary Pharmacokinetics of Immediate and Controlled Release Oxycodone and its Phase I and II Metabolites Using LC-MS-MS.

Oxycodone (OC) is a schedule II semisynthetic opioid in the USA that is prescribed for its analgesic effects and has a high potential for abuse. Prescriptions for OC vary based on the dosage and formulation, immediate release (IR) and controlled release (CR). Monitoring OC metabolites is beneficial for forensic casework. The limited studies that involve pharmacokinetics of the urinary excretion of OC metabolites leave a knowledge gap regarding the excretion of conjugated and minor metabolites, pharmacokinetic differences by formulation, and the impact of CYP2D6 activity on the metabolism and excretion of OC. The objectives of this study were to compare urinary excretion of phase I and II metabolites by formulation and investigate if ratio changes over time could be used to predict the time of intake. Subjects (n = 7) received a single 10mg IR tablet of Oxycodone Actavis. A few weeks later the same subjects received a single 10mg CR tablet of Oxycodone Actavis. During each setting, urine was collected at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48 and 72 h. Urine samples (100 µL) were diluted with 900 µL internal standard mixture and analyzed on an Acquity UPLC® I-class coupled to a Waters Xevo TQD using a previously validated method. The CYP2D6 phenotypes were categorized as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM). Comparisons between IR and CR were performed using two-tailed paired t-test at a significance level of P = 0.05. The metabolite ratios showed a general increase over time. Four metabolite to parent ratios were used to predict the time of intake showing that predictions were best at the early time points.

Mucoadhesive controlled-release formulations containing morin for the control of oral biofilms

This study aimed to evaluate the antimicrobial and anti-biofilm activity of morin on polymicrobial biofilms and its cytotoxicity in controlled-release films and tablets based on gellan gum. Polymicrobial biofilms were formed from saliva for 48 h under an intermittent exposure regime to 1% sucrose and in contact with films or tablets of gellan gum containing 2 mg of morin each. Acidogenicity, bacterial viability, dry weight and insoluble extracellular polysaccharides from biofilms were evaluated. The cytotoxicity of morin was evaluated in oral keratinocytes. Morin released from the systems reduced the viability of all the microbial groups evaluated, as well as the dry weight and insoluble polysaccharide concentration in the matrix and promoted the control of acidogenicity when compared with the control group without the substance. Morin was cytotoxic only at the highest concentration evaluated. In conclusion, morin is an effective agent and shows antimicrobial and anti-biofilm activity against polymicrobial biofilms.

Clinical Demonstrations of Controlled-Release Tablets Constructed by the Combined Usage of Shellac and Hydroxypropyl Methylcellulose

A new tablet system was examined for an intestinal delivery system using hydroxypropyl methylcellulose (HPMC) and shellac. HPMC was incorporated into the inside of the tablet, and shellac was coated on the surface, which was evaluated for its controlled-release property through several dissolution tests, firstly in vitro and then via two kinds of clinical studies with healthy volunteers. The clinical studies were originally designed by employing X-ray photography for the movements of the tablets in the gastrointestinal tract and an electronical device to easily analyze the absorption profile of glucose, a model compound. It was found that the dissolution of the tablet was strongly suppressed in a simulated gastric fluid (pH 1.2) and subsequently started to disintegrate in a simulated intestinal fluid (pH 6.8). The first human study with X-ray photography revealed that the model tablets could pass through the stomach without disintegrating. The controlled release of the tablets was further confirmed via analyses of the AUC, Cmax, and Tmax for the blood glucose concentration with other volunteers. The AUC and Cmax were significantly reduced by using our system, thus concluding that the delivery system combined with the addition of HPMC and a shellac coating unequivocally leads to controlled release in the human gastrointestinal tract.

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer based controlled release tablets of aceclofenac to simultaneously enhance the solubility and bioavailability

The aim of this study was to enhance the solubility of Aceclofenac with a new polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soloplus®) and formulate it in controlled release (CR) tablet dosage form by direct compression method with HPMC K-15. Solid dispersions were prepared in different ratio of Aceclofenac and Soloplus® as F1, F2 and F3 with different polymer ratios i.e. 30%, 50%, and 70% respectively. All the quality control tests were performed for the prepared controlled release tablets. Drug polymer interaction studies of Aceclofenac and Soloplus® were carried using FTIR and XRD. Dissolution study was carried out against Alkaris® as a standard reference. The formulation F3 showed optimum results and followed zero order kinetics. The Soloplus® improved the solubility of the drug and the CR formulation enhanced the delivery in a sustained manner. Hence, the CR formulation enhanced the delivery of aceclofenac in a sustained manner, thereby an efficient drug delivery may lead to an effective anti-inflammatory activity.

Physiologically relevant model to establish the in vivo-in vitro correlation for etamsylate controlled release matrix tablets

BackgroundIn vivo-in vitro correlation (IVIVC) are used during product development for optimization of drug formulations and can serve as a surrogate for bioequivalence studies. AimThis research was performed to investigate the in vitro dissolution and in vivo pharmacokinetics of different etamsylate immediate release (IR), and two controlled release (CR) matrix tablets with different dissolution rates; CRfast and CRslow. Also, to develop a simple physiological model to establish the IVIVC for etamsylate CR tablets. MethodThree different formulations containing 500 mg etamsylate were developed; IR, CRfast, and CRslow tablets. The in vitro dissolution of the IR tablets was examined at different pHs, while the in vitro dissolution of the CR tablets was performed by the buffer transition method, where the pH of the dissolution medium was changed throughout the 12-h dissolution experiment. A group of eight healthy volunteers received one tablet of each formulation, in a three-way cross-over experimental design, with one-week wash-out period between treatments. The pharmacokinetic parameters of etamsylate after the three treatments were estimated. A model that utilized the in vitro dissolution data, the estimated pharmacokinetic parameters after the IR tablets was developed to establish the IVIVC for the CR tablets. ResultsThe in vitro dissolution of the IR tablets showed a pH-dependent dissolution. The plasma concentration-time profile after administration of etamsylate IR tablet followed one-compartment model with first-order absorption and elimination. The maximum concentrations were 7.52 ± 2.1, 3.93 ± 0.96, and 3.13 ± 0.27 mg/L, and the time to achieve the maximum concentration was 5, 8, and 10 h, and the area under the curves were 80.2 ± 13.73, 69.4 ± 12.97, and 61.1 ± 0.44 mg-h/L for the IR, CRfast and CRslow tablets, respectively. There was a good agreement between the model-predicted concentration-time profile and the experimentally observed drug profile after administration of the two CR formulations. The model predicted Cmax and AUC were within 10% of the observed Cmax and AUC. Also, there was very good correlation between the time-scaled % in vivo absorption and the % in vitro dissolution for the two CR matrix tablets, indicating validity of the model. ConclusionThe use of the buffer transition method was appropriate in predicting the in vivo dissolution of the developed CR matrix tablets. The developed model was valid in the establishment of the IVIVC for etamsylate CR tablets.

Formulation and in vitro Evaluation of Effervescent Bilayer Floating Controlled Release Tablets of Clarithromycin and Famotidine

The development of floating tablets with required buoyancy, lag time, and controlling release behaviour of drugs at target site is truly interesting and challenging task for researchers. Current study is concerned with the designing of effervescent floating controlled release tablets of clarithromycin and famotidine to treat peptic ulcer due to Helicobacter pylori (H. pylori) infection. Five formulations (F1-F5) were prepared, among which three formulations were of bilayered tablets while the remaining were included as plain tablets. These tablets were prepared by direct compression method using hydroxypropyl methylcellulose (HPMC) K100M, HPMC K4M and sodium bicarbonate as swelling and floating agents respectively. The qualitative tests such as thickness, hardness, weight variation, friability and uniformity of content were performed to ensure the quality of prepared tablets. The floating lag time of all formulations ranged from 14 to 20 seconds. The effervescent floating tablets with HPMC K4M (F1, F3 &amp; F5) attained the total floating time of more than 12 hours, while tablets prepared with HPMC K100M (F2 &amp; F4) achieved the total floating time of less than 7 hours. This difference in floating behaviour could be due to the variation in compaction and flow properties of the two polymers. The formulations with HPMC K100M (F2 &amp; F4) have comparatively more sustained drug release properties when compared to F1, F3 and F4 using HPMC K4M as swelling and floating polymers. This could be attributed to better compaction of HPMC K100M. The prepared tablets follow non-Fickian diffusion kinetics. Overall, these floating controlled release effervescent bilayer and plain tablets may enhance the compliance and therapeutic outcomes of clarithromycin and famotidine in treatment of H. pylori.

Evaluation of Metformin Hydrochloride Floating Drug Delivery System: In vitro Study and In vivo Prediction

Aim: This research work was aimed to evaluate Metformin hydrochloride (MH) floating dosage form by In vitro evaluation/In vivo prediction and to evaluate it’s predictability through it’s application during the R&amp;D using Insilico technique in WINONLIN Software. MH was examined as a model drug, which is a biguanide and is an hypoglycemic agent administered orally. The study was aimed to determine the the systemic concentrations of MH using In-vivo prediction.&#x0D; Study Design: Fabrication and assessment of Metformin hydrochloride floating drug delivery system: In Vitro evaluation /In Vivo prediction. Biorelevant media was selected for dissolution profile of 12 units of dosage form. Software assisted program used for data feeding and results output.&#x0D; Methodology: The absorption window for MH is the upper portion of the small gut in which the GI absorption is complete after 6 h. Hence gastroretentive formulation was developed and validity of dissolution study was extended by In vivo pharmacokinetic prediction using WinNonlin Software. A mechanistic oral absorption model was built in Phoenix WinNonlin® software.&#x0D; In the presented work, significant yet crucial, gastrointestinal (GI) variables are considered for biopredictive dissolution testing to account for a valuable input for physiologically-based pharmacokinetic (PBPK) platform programs. While simulations are performed and mechanistic insights are gained from such simulations from the WinNonlin program.&#x0D; Results: These floating tablets were observed for In vitro release and studied for In vivo pharmacokinetic prediction. From the obtained values, a meaningful In vivo prediction was done. interestingly from the results attained floating tablets showed sustained drug release and extended drug absorbed in 24h. Fascinatingly, from the data it was proved that drug formulation resides for desired time. The absorption of MH from the developed CR tablet was 1.4 fold higher than its marketed tablet and it had higher AUC0–t values than the marketed product which indicates superior bioavailability of test product compared to marketed tablet with similar dose in Invivo pharmacokinetic prediction. The mean value of biological half-life (t1/2) and Tmax of MH from test formulation is two times more, Test product has shown higher MRT, showing that the drug is maintained longer in the body in comparison to marketed product indicates controlled absorption.&#x0D; Conclusion: Here we concluded that, a comparative prediction pharmacokinetic evaluation of the fabricated controlled release tablets and the marketed formulation indicates that the fabricated controlled release tablets are well absorbed and the degree of absorption is greater than that of the marketed ER formulation with larger gastric residence time.