scholarly journals In-vitro Study and In-vivo Predictions of Valsartan and Amlodipine Capsules through Micro Tablets

2021 ◽  
pp. 335-349
Author(s):  
K. Binuraj ◽  
Maya Sharma ◽  
Sandip Zine
Keyword(s):  
Prediction Error ◽  
Oral Absorption ◽  
Reference Product ◽  
Research Work ◽  
In Vitro Dissolution ◽  
Prediction Errors ◽  
Test Product ◽  
Dissolution Studies

Aim: The present research work was carried out to develop Valsartan and Amlodipine capsules using micro tablets and to evaluate the in-vitro drug release characteristics. The study was targeted to determine the systemic concentrations using in-vivo prediction. Study Design: The in vivo parameters along with the marketed Valsartan and Amlodipine product was predicted using WinNonlin® software external prediction method. Place and Duration of the Study: The present work was carried out at Pacific Academy of Higher Education and Research University, Udaipur between the duration of February-2019 to November-2019. Methodology: The dissolution studies were performed for test and reference products in 900ml Phosphate buffer (pH 6.8), and the USP Type II apparatus at 50 RPM with a sinker. The in vivo pharmacokinetic prediction was performed using WinNonlin® Software. A mechanistic oral absorption model was built in Phoenix® WinNonlin® 8.2 software (Certara, Princeton, NJ, 08540, USA). Results: The in-vitro dissolution studies were comparable between the test product and the reference product. The Similarity factor achieved was 61.7 and 84.8 for Amlodipine and Valsartan test product in comparison with the reference product. An average percent prediction error for Cmax and AUC for both Valsartan and Amlodipine achieved was less than 10% for all IVIVC models. Conclusion: The relatively low prediction errors for Cmax and AUC observed strongly suggest that the Valsartan and Amlodipine IVIVC models are valid. The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies.

scholarly journals An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 507
Author(s):  
Isabel Gonzalez-Alvarez ◽  
Marival Bermejo ◽  
Yasuhiro Tsume ◽  
Alejandro Ruiz-Picazo ◽  
Marta Gonzalez-Alvarez ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
In Vitro Dissolution ◽  
Case Examples ◽  
Dissolution Studies ◽  
Weak Bases ◽  
Transit Times ◽  
Class Iib ◽  
The Impact

The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia® as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions were compared with the results from previous bioequivalence (BE) human studies. Product dissolution studies were performed using a computer-controlled multicompartmental dissolution device (GIS) equipped with three dissolution chambers, representing stomach, duodenum, and jejunum, with integrated transit times and secretion rates. The measured dissolved amounts were modelled in each compartment with a set of differential equations representing transit, dissolution, and precipitation processes. The observed drug concentration by in vitro dissolution studies were directly convoluted with permeability and disposition parameters from literature to generate the predicted plasma concentrations. The GIS was able to detect the dissolution differences among reference and generic formulations in the gastric chamber where the drug solubility is high (pH 2) while the USP 2 standard dissolution test at pH 2 did not show any difference. Therefore, the current study confirms the importance of multicompartmental dissolution testing for weak bases as observed for other case examples but also the impact of excipients on duodenal and jejunal in vivo behavior.

scholarly journals Development of Level A In Vitro–Vivo Correlation for Electrosprayed Microspheres Containing Leuprolide: Physicochemical, Pharmacokinetic, and Pharmacodynamic Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 36
Author(s):  
Dong-Seok Lee ◽  
Dong Wook Kang ◽  
Go-Wun Choi ◽  
Han-Gon Choi ◽  
Hea-Young Cho
Keyword(s):  
Plasma Concentration ◽  
Prediction Error ◽  
Subcutaneous Administration ◽  
In Vitro Dissolution ◽  
Burst Release ◽  
Maximum Plasma ◽  
Time Curve ◽  
In Vivo Dissolution

This study optimized the preparation of electrosprayed microspheres containing leuprolide and developed an in vitro–in vivo correlation (IVIVC) model that enables mutual prediction between in vitro and in vivo dissolution. The pharmacokinetic (PK) and pharmacodynamic (PD) study of leuprolide was carried out in normal rats after subcutaneous administration of electrosprayed microspheres. The parameters of the IVIVC model were estimated by fitting the PK profile of Lucrin depot® to the release compartment of the IVIVC model, thus the in vivo dissolution was predicted from the in vitro dissolution. From this correlation, the PK profile of leuprolide was predicted from the results of in vivo dissolution. The IVIVC model was validated by estimating percent prediction error (%PE) values. Among prepared microspheres, an optimal formulation was selected using the IVIVC model. The maximum plasma concentration and the area under the plasma concentration–time curve from zero to infinity from the predicted PK profile were 4.01 ng/mL and 52.52 h·ng/mL, respectively, and from the observed PK profile were 4.14 ng/mL and 56.95 h·ng/mL, respectively. The percent prediction error values of all parameters did not exceed 15%, thus the IVIVC model satisfies the validation criteria of the Food and Drug Administration (FDA) guidance. The PK/PD evaluation suggests that the efficacy of OL5 is similar to Lucrin depot®, but the formulation was improved by reducing the initial burst release.

scholarly journals Formulation and Pharmacokinetic Evaluation of Ritonavir Floating Tablets in the Management of AIDS

2018 ◽  
Vol 10 (6) ◽  
Author(s):  
R. Shireesh Kiran ◽  
B. Chandra Shekar ◽  
B. Nagendra Babu
Keyword(s):  
Drug Release ◽  
Sodium Bicarbonate ◽  
Controlled Drug Release ◽  
In Vitro Dissolution ◽  
Gastric Residence Time ◽  
Dissolution Studies ◽  
Floating Tablet ◽  
Gastro Retentive

In the current study, gastro-retentive tablets of Ritonavir was developed to increase its oral bioavailability using hydrophilic polymers HPMC K 4M, K 15M, and K 100M as release retarding agents. Polyox WSR 303 was chosen as resin, sodium bicarbonate was used as effervescent agents. The tablets were prepared by direct compression method and FTIR studies revealed that there is no interaction between the drug and polymers used for the formulation. Among all the formulations F21 containing HPMC K 100M, Crospovidone, Polyox WSR 303 and sodium bicarbonate, as gas generating agent was choosen as optimized formulation based on the evaluation parameters, floating lag time (33 sec) and total floating time (>24 h) and in vitro dissolution studies. From in vitro dissolution studies, the optimized formulation F21 and marketed product was shown 98.67% and 95.09 ± 5.01% of drug release respectively. From in vivo bioavailability studies, after oral administration of floating tablet containing 100 mg Ritonavir, the Cmax, Tmax, and AUC0–∞ of optimized gastroretentive formulation were found to be 30.11 ± 1.16μg/mL, 8.00±1.23 h and 173 ± 26.34μg*h/ml, respectively. Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for improved bioavailability.

INVESTIGATION OF SOLUBILITY ENHANCEMENT OF PRASUGREL HYDROCHLORIDE: NANOSUSPENSIONS AND CYCLODEXTRIN INCLUSION COMPLEXES

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (02) ◽  
pp. 29-38
Author(s):  
R. K Devara ◽  
◽  
P. Reddipogu ◽  
S Kumar ◽  
B. Rambabu ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Oral Bioavailability ◽  
Oral Absorption ◽  
In Vitro Dissolution ◽  
Precipitation Method ◽  
Formulation Development ◽  
Pure Drug

The objective of this study was to investigate nanosuspensions, hydroxypropyl-β-cyclodextrin (HPβCD) complexes and SLS powders for enhancing the solubility and dissolution rate of Prasugrel HCl (PHCl) so as to reduce the fluctuations in its oral bioavailability. PHCl nanosuspensions were prepared using evaporative precipitation method. HPβCD inclusion complexes of PHCl were prepared using physical mixture, co-evaporation and kneading methods. Powders of the pure drug with different SLS amounts were prepared. The formulations were characterized using techniques such as powder x-ray diffractometry, scanning electron microscopy, in vitro dissolution and in vivo absorption in rats. To further aid in the betterment of development of nevirapine nanosuspension, in vitro in vivo correlation (IVIVC) was established using deconvolution technique. Nanosuspensions and HPβCD inclusion complexes of PHCl were successfully prepared. The dissolution rate and oral absorption of PHCl in the form of nanosuspensions was significantly higher than that of HPβCD complexes, SLS powders as well as pure drug. All the techniques investigated in this study can be used to enhance dissolution rate and oral absorption of prasugrel HCl and thus can reduce the fluctuations in its oral bioavailability. Nanosuspensions demonstrated to be better and superior technique when compared to other techniques investigated in enhancing oral bioavailability of PHCl. IVIVC that could aid in further formulation development of PHCl nanosuspension was successfully developed using a deconvolution approach.

Enhancement of in vitro dissolution and in vivo performance/oral absorption of FEB-poloxamer-TPGS solid dispersion

2018 ◽  
Vol 46 ◽  
pp. 408-415 ◽  
Author(s):  
Xiaoxia Sheng ◽  
Jingjing Tang ◽  
Jiayin Bao ◽  
Xiangjun Shi ◽  
Weike Su
Keyword(s):  
Solid Dispersion ◽  
Oral Absorption ◽  
In Vitro Dissolution

scholarly journals Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1210
Author(s):  
Sultan Alshehri ◽  
Abdullah Alanazi ◽  
Ehab M. Elzayat ◽  
Mohammad A. Altamimi ◽  
Syed S. Imam ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Solid Dispersions ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
In Vivo Evaluation ◽  
Significant Release

Gefitinib (Gef) is a poorly water-soluble antitumor drug, which shows poor absorption/bioavailability after oral administration. Therefore, this study was carried out to develop Gef solid dispersions (SDs) using different carriers and different techniques in order to enhance its dissolution and oral absorption/bioavailability. Various SD formulations of Gef were established using fusion and microwave methods utilizing Soluplus, Kollidone VA64, and polyethylene glycol 4000 (PEG 4000) as the carriers. Developed SDs of Gef were characterized physicochemically and evaluated for in vitro dissolution and in vivo pharmacokinetic studies. The physicochemical evaluation revealed the formation of Gef SDs using fusion and microwave methods. In vitro dissolution studies indicated significant release of Gef from all SDs compared to the pure Gef. Optimized SD of Gef (S2-MW) presented significant release of Gef (82.10%) compared with pure Gef (21.23%). The optimized Gef SD (S2) was subjected to in vivo pharmacokinetic evaluation in comparison with pure Gef in rats. The results indicated significant enhancement in various pharmacokinetic parameters of Gef from an optimized SD S2 compared to the pure Gef. In addition, Gef-SD S2 resulted in remarkable improvement in bioavailability compared to the pure Gef. Overall, this study suggested that the prepared Gef-SD by microwave method showed marked enhancement in dissolution and bioavailability.

scholarly journals Efficient validated method of HPLC to determine amlodipine in combinated dosage form containing amlodipine, enalapril and bisoprolol and in vitro dissolution studies with in vitro/ in vivo correlation

Pharmacia ◽  
2020 ◽  
Vol 67 (2) ◽  
pp. 55-61
Author(s):  
Liliya Logoyda
Keyword(s):  
Dosage Form ◽  
Hplc Method ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Buffer Solution ◽  
Pharmaceutical Dosage Form ◽  
Dissolution Studies ◽  
Ultraviolet Detector

Aim. A rapid and reproducible HPLC method has been developed for the determination of amlodipine in experimental combined dosage forms containing amlodipine, bisoprolol and enalapril and for drug dissolution studies. Materials and methods. The separation was done using a column Phenomenex Polar Synergi, 5 μm, 4.6×50 mm and a mobile phase of methanol:phosphate buffer solution (65:35, v/v), flow-rate of 1.0 mL/min. The injection volume was 100 μL and the ultraviolet detector was set at 240 nm. Results. The method was validated as per ICH guidelines. Under these conditions, amlodipine was eluted at 1.89 min. Total run time was shorter than 2.5 min. The linearity of the method had a good correlation with concentration and peak area. The correlation coefficient of amlodipine was found to be not less than 0.9991, which indicates good linear relationship over concentration range 0.625 mg/mL–5.000 mg/mL (1.250 mg/mL–5.000 mg/mL at pH 4.5). The % RSD values in intra-day and inter-day precision study were found to be less than 0.267 for amlodipine, which indicate method was precise. Hence, the present developed method was said to be suitable for the analysis of drugs in their pharmaceutical dosage form. Also, in vitro dissolution of amlodipine containing tablets were performed to validate the suitability of the proposed method. The dissolution pattern complies with the FDA standards, indicating suitability of the proposed method for the dissolution study of amlodipine. It will allow conducting comparative studies in vitro to confirm the equivalence of tablets containing amlodipine. Conclusion. A simple and sensetive HPLC method was developed for the estimation of amlodipine in tablets containing amlodipine, enalapril and bisoprolol. The proposed method was applied successfully for quality control assay of amlodipine in experimental tablets and in vitro dissolution studies. In vitro / in vivo correlation of amlodipine has been conducted.

Acceleration of in vitro dissolution studies of sustained release dosage form of theophylline and in vitro–in vivo evaluations in terms of correlations

2011 ◽  
Vol 36 (4) ◽  
pp. 243-248 ◽  
Author(s):  
Gökhan Ertan ◽  
Ercüment Karasulu ◽  
Işık Özgüney ◽  
Yeşim Karasulu ◽  
Şebnem Apaydın ◽  
...  
Keyword(s):  
Sustained Release ◽  
Dosage Form ◽  
In Vitro Dissolution ◽  
Dissolution Studies

Evaluation of In Vitro Dissolution and In Vivo Oral Absorption of Drug Nanopowders Prepared by Novel Wet-Milling Equipment

2010 ◽  
Vol 6 (6) ◽  
pp. 571-576 ◽  
Author(s):  
Yusuke Tanaka ◽  
Mitsugi Inkyo ◽  
Ryoko Yumoto ◽  
Junya Nagai ◽  
Mikihisa Takano ◽  
...  
Keyword(s):  
Oral Absorption ◽  
In Vitro Dissolution ◽  
Wet Milling ◽  
Milling Equipment

scholarly journals DEVELOPMENT AND IN VITRO–IN VIVO EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF AN ANTIRETROVIRAL AGENT RITONAVIR

2019 ◽  
pp. 436-443
Author(s):  
SHIREESH KIRAN R ◽  
CHANDRA SHEKAR B ◽  
NAGENDRA BABU B
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Extended Release ◽  
In Vitro Dissolution ◽  
Floating Tablets ◽  
Gastric Residence Time ◽  
Dissolution Studies ◽  
Evaluation Parameters

Objective: The present research work concerns the development of the extended release of Ritonavir floating matrix tablets, designed to prolong the gastric residence time, increase the drug bioavailability, and diminish the side effects of irritating drugs. Methods: The floating tablets of Ritonavir were prepared by direct compression method using different grades of hydroxypropyl methylcellulose (HPMC), crospovidone, Polyox WSR 303, and sodium bicarbonate, as gas generating agent. Evaluation parameters and in vivo radiographic studies were conducted in suitable model. Results: Among all formulations, F21 was chosen as optimized formulation based on evaluation parameters such as floating lag time (33 s), total floating time (>24 h), and in vitro dissolution studies. From in vitro dissolution studies, the optimized formulation F21 and marketed product were shown 98.67% and 91.46±5.02% of drug release, respectively. The main appliance of medication discharge follows zero-order kinetics and non- Fickian transport by coupled diffusion and erosion. In vivo experiments maintained the potentials in extending the gastric residence time in the fasted state in beagle dogs. The mean gastric residence time of the optimized formulation found to be 330 min±40 in the stomach, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for enhanced bioavailability. Conclusion: From in vitro and in vivo radiographic studies, Ritonavir floating tablets estimated to provide novel choice for harmless, inexpensive, and extended release for the effective management of AIDS.

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