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

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 A Mechanistic Physiologically-Based Biopharmaceutics Modeling (PBBM) Approach to Assess the In Vivo Performance of an Orally Administered Drug Product: From IVIVC to IVIVP

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 74 ◽  
Author(s):  
Marival Bermejo ◽  
Bart Hens ◽  
Joseph Dickens ◽  
Deanna Mudie ◽  
Paulo Paixão ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Drug Product ◽  
Continuous Optimization ◽  
In Vitro Dissolution ◽  
Oral Drug ◽  
Dissolution Testing ◽  
Bicarbonate Buffer ◽  
Physiologically Based

The application of in silico modeling to predict the in vivo outcome of an oral drug product is gaining a lot of interest. Fully relying on these models as a surrogate tool requires continuous optimization and validation. To do so, intraluminal and systemic data are desirable to judge the predicted outcomes. The aim of this study was to predict the systemic concentrations of ibuprofen after oral administration of an 800 mg immediate-release (IR) tablet to healthy subjects in fasted-state conditions. A mechanistic oral absorption model coupled with a two-compartmental pharmacokinetic (PK) model was built in Phoenix WinNonlinWinNonlin® software and in the GastroPlus™ simulator. It should be noted that all simulations were performed in an ideal framework as we were in possession of a plethora of in vivo data (e.g., motility, pH, luminal and systemic concentrations) in order to evaluate and optimize these models. All this work refers to the fact that important, yet crucial, gastrointestinal (GI) variables should be integrated into biopredictive dissolution testing (low buffer capacity media, considering phosphate versus bicarbonate buffer, hydrodynamics) to account for a valuable input for physiologically-based pharmacokinetic (PBPK) platform programs. While simulations can be performed and mechanistic insights can be gained from such simulations from current software, we need to move from correlations to predictions (IVIVC → IVIVP) and, moreover, we need to further determine the dynamics of the GI variables controlling the dosage form transit, disintegration, dissolution, absorption and metabolism along the human GI tract. Establishing the link between biopredictive in vitro dissolution testing and mechanistic oral absorption modeling (i.e., physiologically-based biopharmaceutics modeling (PBBM)) creates an opportunity to potentially request biowaivers in the near future for orally administered drug products, regardless of its classification according to the Biopharmaceutics Classification System (BCS).

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.

Significance of In-Vitro and In-Vivo Correlation in Drug Delivery System

2018 ◽  
Vol 4 (4) ◽  
pp. 523-531
Author(s):  
Hina Mumtaz ◽  
Muhammad Asim Farooq ◽  
Zainab Batool ◽  
Anam Ahsan ◽  
Ashikujaman Syed
Keyword(s):  
Dosage Form ◽  
Pharmaceutical Preparations ◽  
Pharmacokinetic Profile ◽  
In Vitro Dissolution ◽  
Time Saving ◽  
Pharmaceutical Dosage Form ◽  
Short Period ◽  
Form Development

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

Biopharmaceutical and Preclinical Studies of Zaleplon as Semisolid Dispersions with Self-emulsifying Lipid Surfactants for Oral Delivery

1970 ◽  
Vol 9 (1) ◽  
pp. 3102-3111
Author(s):  
Narendar Dudhipala ◽  
Arjun Narala ◽  
Dinesh Suram ◽  
Karthik Yadav Janga
Keyword(s):  
Oral Delivery ◽  
Molecular State ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Phase Solubility ◽  
Microscopic Studies ◽  
Pure Drug

The objective of this present study is to develop a semisolid dispersion (SSD) of zaleplon with the aid of self-emulsifying lipid based amphiphilic carriers (TPGS E or Gelucire 44/14) addressing the poor solubility of this drug. A linear relationship between the solubility of drug with respect to increase in the concentration of lipid surfactant in aqueous medium resulting in AL type phase diagram was observed from phase solubility studies. Fusion method was employed to obtain semisolid dispersions (SSD) of zaleplon which showed high content uniformity of drug. The absence of chemical interactions between the pure drug, excipients and formulations were conferred by Fourier transmission infrared spectroscopic examinations. The photographic images from polarized optical microscopic studies revealed the change in crystalline form of drug to amorphous or molecular state. The superior dissolution parameters of zaleplon from SSD over pure crystalline drug interpreted from in vitro dissolution studies envisage the ability of these lipid surfactants as solubility enhancers. Further, the caliber of TPGS E or Gelucire 44/14 in encouraging the GI absorption of drug was evident with the higher human effective permeability coefficient and fraction oral dose of drug absorbed from SSD in situ intestinal permeation study. In conclusion, in vivo studies in Wister rats demonstrated an improvement in the oral bioavailability of zaleplon from SSD over control pure drug suspension suggesting the competence of Gelucire 44/14 and TPGS E as conscientious carriers to augment the dissolution rate limited bioavailability of this active

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

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