Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats

The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin® US2 at 1:1 and 1:2 ratios. Various CN-SDs were prepared using freeze drying and microwave technologies. The developed SDs were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). In-vitro dissolution studies were conducted to evaluate CN formulations at pH 6.8. Drug-free S-SNEDDSs showed acceptable self-emulsification and powder flow properties. DSC and XRD showed that CN was successfully amorphized into SDs. The combination of drug-free S-SNEDDS + pure CN showed negligible drug dissolution due to poor CN migration into the formed nanoemulsion droplets. CN-SDs and drug-loaded S-SNEDDS showed only 4% and 23% dissolution efficiency (DE) while (drug-free S-SNEDDS + FD-SD) combination showed 880% and 160% enhancement of total drug release compared to uncombined SD and drug-loaded S-SNEDDS, respectively. (Drug-free S-SNEDDS + SD) combination offer a potential approach to overcome the negative impact of hypochlorhydria/achlorhydria on drug absorption by enhancing dissolution at elevated pH environments. In addition, the systems minimize the adverse effect of adsorbent on drug release.

Download Full-text

In-Vivo Analysis and Model-Based Prediction of Tensides’ InFluence on Drug Absorption

Molecules ◽

10.3390/molecules26185602 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5602

Author(s):

Zuzana Vitková ◽

Marián Tárník ◽

Jarmila Pavlovičová ◽

Ján Murgaš ◽

Andrej Babinec ◽

...

Keyword(s):

Drug Absorption ◽

Fold Increase ◽

In Vitro Dissolution ◽

Absolute Bioavailability ◽

Model Based ◽

Rate Of Absorption ◽

In Vivo Analysis ◽

Per Oral

Depending on their concentrations the surface-active substances, tensides (surfactants) can positively or negatively influence the drug absorption, which is widely used in the design of the dosage forms with controlled release. A problem is that the (in-vivo) rate of absorption cannot be directly measured and for that reason, it is frequently substituted by evaluation of the (in-vitro) dissolution. On other hand, a suitably designed pharmacokinetic model can directly predict virtually all pharmacokinetic quantities including both the rate of absorption and fraction of the dose reaching the blood circulation. The paper presents a new approach to the analysis of the rate of drug absorption and shows its superiority over traditional in-vivo approaches. Both the in-vivo analysis and model-based prediction of the tenside (monolaurin of sucrose) influence on the rate of absorption of the drug (sulfathiazole) after instantaneous per-oral administration to rats are discussed. It was found that 0.001% solution of tenside can increase the rate of absorption by cca 50% and a two-fold increase in absolute bioavailability can be reached. Attention is also devoted to the formal requirements laid on the model’s structure and its identifiability. The systematic design, substantiation and validation of a parsimonious predictive model that confirms in-vivo results are presented. The match between in-vivo observations and model-based predictions is demonstrated. The frequently overlooked metaphysics lying behind the compartmental modelling is briefly explained.

Download Full-text

Beryllium Metal Solubility in the Lung, Comparison of Metal and Hot-pressed Forms by in vivo and in vitro Dissolution Bioassays

Human Toxicology ◽

10.1177/096032718700600311 ◽

1987 ◽

Vol 6 (3) ◽

pp. 233-240 ◽

Cited By ~ 25

Author(s):

S. André ◽

H. Métivier ◽

G. Lantenois ◽

M. Boyer ◽

D. Nolibé ◽

...

Keyword(s):

Occupational Safety ◽

In Vitro Models ◽

In Vitro Dissolution ◽

In Vivo Model ◽

Health Administration ◽

In Vivo Experiments ◽

Safety And Health ◽

Dissolution Model

The solubility of two industrial forms of beryllium, i.e. particles of metal powder and particles of hot-pressed beryllium, was investigated using in vivo and in vitro models. In the in vivo model, baboons and rats were used and were injected via the trachea with amounts of beryllium equivalent to 100, 500 and 1000 fold the maximum permissible concentration (MPC) recommended by the US Occupational Safety and Health Administration. In vivo experiments showed that in both species the daily beryllium solubility rates were about 5 x 10-6 for metal particles and that in rats the daily beryllium solubility rate was about 5 x 10-5 for the hot-pressed particles. During the 10 months of the experiment with baboons, urinary excretion of beryllium was proportional to the amount administered. With regard to results for the in vitro models, the outcome of the acellular dissolution test using a serum simulant was not consistent with the in vivo results, though a cellular model using cultured macrophages showed the same trends in the dissolution rates for the two forms of beryllium as those observed in vivo. This result suggests that a cellular rather than an acellular dissolution model would be better at predicting solubility of beryllium compounds in the lungs.

Download Full-text

Luminal Fluid Motion Inside an In Vitro Dissolution Model of the Human Ascending Colon Assessed Using Magnetic Resonance Imaging

Pharmaceutics ◽

10.3390/pharmaceutics13101545 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1545

Author(s):

Connor O’Farrell ◽

Caroline L. Hoad ◽

Konstantinos Stamatopoulos ◽

Luca Marciani ◽

Sarah Sulaiman ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Dosage Form ◽

In Vitro Dissolution ◽

Ascending Colon ◽

Resonance Imaging ◽

Dissolution Model ◽

Luminal Flow

Knowledge of luminal flow inside the human colon remains elusive, despite its importance for the design of new colon-targeted drug delivery systems and physiologically relevant in silico models of dissolution mechanics within the colon. This study uses magnetic resonance imaging (MRI) techniques to visualise, measure and differentiate between different motility patterns within an anatomically representative in vitro dissolution model of the human ascending colon: the dynamic colon model (DCM). The segmented architecture and peristalsis-like contractile activity of the DCM generated flow profiles that were distinct from compendial dissolution apparatuses. MRI enabled different motility patterns to be classified by the degree of mixing-related motion using a new tagging method. Different media viscosities could also be differentiated, which is important for an understanding of colonic pathophysiology, the conditions that a colon-targeted dosage form may be subjected to and the effectiveness of treatments. The tagged MRI data showed that the DCM effectively mimicked wall motion, luminal flow patterns and the velocities of the contents of the human ascending colon. Accurate reproduction of in vivo hydrodynamics is an essential capability for a biorelevant mechanical model of the colon to make it suitable for in vitro data generation for in vitro in vivo evaluation (IVIVE) or in vitro in vivo correlation (IVIVC). This work illustrates how the DCM provides new insight into how motion of the colonic walls may control luminal hydrodynamics, driving erosion of a dosage form and subsequent drug release, compared to traditional pharmacopeial methods.

Download Full-text

In Vitro Dissolution Model Can Predict the in Vivo Taste Masking Performance of Coated Multiparticulates

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.9b00060 ◽

2019 ◽

Vol 16 (5) ◽

pp. 2095-2105 ◽

Cited By ~ 3

Author(s):

Alexander Keeley ◽

Minyi Teo ◽

Zarina Ali ◽

John Frost ◽

Manish Ghimire ◽

...

Keyword(s):

In Vitro Dissolution ◽

Taste Masking ◽

Dissolution Model

Download Full-text

Mechanistic study on hydrodynamics in the mini-scale biphasic dissolution model and its influence on in vitro dissolution and partitioning

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2018.09.005 ◽

2018 ◽

Vol 124 ◽

pp. 328-338 ◽

Cited By ~ 3

Author(s):

Kathrin Locher ◽

Jens M. Borghardt ◽

Herbert Wachtel ◽

Kerstin J. Schaefer ◽

Karl G. Wagner

Keyword(s):

In Vitro Dissolution ◽

Mechanistic Study ◽

Dissolution Model

Download Full-text

Selective LC determination of cabergoline in the bulk drug and in tablets: In vitro dissolution studies

Chromatographia ◽

10.1016/s0009-5893(07)82061-3 ◽

2007 ◽

Vol 65 (9-10) ◽

pp. 561-567

Author(s):

A ONAL ◽

O SAGIRLI ◽

D SENSOY

Keyword(s):

In Vitro Dissolution ◽

Dissolution Studies ◽

Bulk Drug

Download Full-text

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

Research in Pharmacy and Health Sciences ◽

10.32463/rphs.2018.v04i04.23 ◽

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.

Download Full-text

The Artificial Stomach and Duodenum (ASD): A physiologically relevant in vitro dissolution tool

10.3390/ecps2012-00797 ◽

2012 ◽

Author(s):

Shobha Bhattachar ◽

Lee Burns

Keyword(s):

In Vitro Dissolution

Download Full-text

Gastroretentive System of Fluvastatin Sodium by Using Natural Mucilage and Synthetic Polymer

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v4i2.8856 ◽

2014 ◽

Vol 4 (2) ◽

Author(s):

Umamaheswara G. ◽

Anudeep D.

Keyword(s):

Half Life ◽

Release Kinetics ◽

Kinetic Studies ◽

Diffusion Path ◽

Synthetic Polymer ◽

In Vitro Dissolution ◽

Direct Compression ◽

Drug Content ◽

Biological Half Life

Fluvastatin sodium is a novel compound used as cholesterol lowering agent which acts through the inhibition of 3- hydroxyl-3- methyl glutaryl- coenzyme A (HMG-Co A) reductase. It has short biological half life (1-3h) in humans required a dosing frequency of 20 to 40mg twice a day. Due to its short variable biological half life it has been developed to a sustained gastroretentive system with a natural and synthetic polymer and to study how far the natural mucilage improves the sustained activity. Floating tablets were prepared by direct compression method using in combination of natural mucilage and synthetic polymer. Prior to the preparation of tablets the physical mixtures were subjected to FT IR studies and pre compression parameters. After preparation of tablets they were subjected to various tests like swollen index, drug content, In vitro dissolution and release kinetics with pcp disso software etc. The tablets prepared by direct compression shown good in thickness, hardness and uniformity in drug content, the prepared tablets floated more than 12h except FS1 and FS2 shows 9 and 11h. Swollen index studies shows with increase in concentration of polymer the swelling increases the diffusion path length by which the drug molecule may have to travel and cause lag time. In vitro results shows that on increasing the amount of hibiscus polymer the sustain activity is increased because of its integrity and forms a thick swollen mass and reduces the erosion property of the HypromelloseK100M, kinetic studies shows that FS 1, FS2, FS3 followed the Korsmeyer peppas model and the rest FS 4, FS 5, FS6 follows the zero order respectively. Based on n value indicating that the drug release followed super case II transport mechanism due to the erosion of the polymer.

Download Full-text