Microfluidic Measurements of Drug Dissolution Using a Quartz Crystal Microbalance

2016 ◽  
Author(s):  
Shelly Gulati ◽  
Janpierre A. Bonoan ◽  
Kylee V. Schesser ◽  
Joshua F. Arucan ◽  
Xiaoling Li
Keyword(s):  
Benzoic Acid ◽  
Quartz Crystal Microbalance ◽  
Quartz Crystal ◽  
Rapid Test ◽  
The Body ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
Dissolution Testing ◽  
Testing Method

This work describes a microfluidic drug dissolution testing method that was developed using a commercial quartz crystal microbalance (QCM) resonator combined with an axial microfluidic flow cell. Dissolution testing is used to obtain temporal dissolution profiles of drugs, which provide information on the bioavailability or the drug’s ability to be completely dissolved and then absorbed and utilized by the body. Feasibility of the QCM dissolution testing method was demonstrated using a sample drug system of thin films of benzoic acid dissolved in water, capturing the drug dissolution profile under different microflow conditions. Our analysis method uses the responses of resonance frequency and resistance of the quartz crystal during dissolution testing to determine the characteristic profiles of benzoic acid dissolved over a range of microflows (10–1000 μL/min). The initial dissolution rates were obtained from the characteristic profiles and found to increase with higher flow rates. This aligns with the expected trend of increased dissolution with higher hydrodynamic forces. The QCM-based microfluidic drug dissolution testing method has advantages over conventional dissolution test methods, including reduced sample sizes, rapid test durations, low resource requirements, and flow conditions that more closely model in vivo conditions.

scholarly journals Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhongmei Chi ◽  
Irfan Azhar ◽  
Habib Khan ◽  
Li Yang ◽  
Yunxiang Feng
Keyword(s):  
High Speed ◽  
Sequential Analysis ◽  
Immediate Release ◽  
Drug Dissolution ◽  
High Temporal Resolution ◽  
Dissolution Profile ◽  
Dissolution Testing ◽  
Combination Drug ◽  
Efficient Separation ◽  
High Efficient

AbstractDissolution testing plays many important roles throughout the pharmaceutical industry, from the research and development of drug products to the control and evaluation of drug quality. However, it is a challenging task to perform both high-efficient separation and high-temporal detection to achieve accurate dissolution profile of each active ingredient dissolved from a drug tablet. In our study, we report a novel non-manual-operation method for performing the automatic dissolution testing of drug tablets, by combining a program-controlled sequential analysis and high-speed capillary electrophoresis for efficient separation of active ingredients. The feasibility of the method for dissolution testing of real drug tablets as well as the performance of the proposed system has been demonstrated. The accuracy of drug dissolution testing is ensured by the excellent repeatability of the sequential analysis, as well as the similarity of the evaluation of dissolution testing. Our study show that the proposed method is capable to achieve simultaneous dissolution testing of multiple ingredients, and the matrix interferences can be avoided. Therefore it is of potential valuable applications in various fields of pharmaceutical research and drug regulation.

scholarly journals Protein Adsorption to Titanium and Zirconia Using a Quartz Crystal Microbalance Method

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
You Kusakawa ◽  
Eiji Yoshida ◽  
Tohru Hayakawa
Keyword(s):  
Surface Roughness ◽  
Protein Adsorption ◽  
Quartz Crystal Microbalance ◽  
Quartz Crystal ◽  
Adsorption Rate ◽  
Force Microscopy ◽  
Atomic Force ◽  
A Cell ◽  
Addition Amount

Protein adsorption onto titanium (Ti) or zirconia (ZrO2) was evaluated using a 27 MHz quartz crystal microbalance (QCM). As proteins, fibronectin (Fn), a cell adhesive protein, and albumin (Alb), a cell adhesion-inhibiting protein, were evaluated. The Ti and ZrO2 sensors for QCM were characterized by atomic force microscopy and electron probe microanalysis observation, measurement of contact angle against water, and surface roughness. The amounts of Fn and Alb adsorbed onto the Ti and ZrO2 sensors and apparent reaction rate were obtained using QCM measurements. Ti sensor showed greater adsorption of Fn and Alb than the ZrO2 sensor. In addition, amount of Fn adsorbed onto the Ti or ZrO2 sensors was higher than that of Alb. The surface roughness and hydrophilicity of Ti or ZrO2 may influence the adsorption of Fn or Alb. With regard to the adsorption rate, Alb adsorbed more rapidly than Fn onto Ti. Comparing Ti and ZrO2, Alb adsorption rate to Ti was faster than that to ZrO2. Fn adsorption will be effective for cell activities, but Alb adsorption will not. QCM method could simulate in vivo Fn and Alb adsorption to Ti or ZrO2.

Dissolution profiles of fenbendazole from binary solid dispersions: a mathematical approach

2021 ◽  
Author(s):  
María Elisa Melian ◽  
Cintia Alejandra Briones Nieva ◽  
Laura Domínguez ◽  
Elio Emilio Gonzo ◽  
Santiago Palma ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
Lumped Model ◽  
Initial Release ◽  
Pure Drug ◽  
Physical Mixtures ◽  
Main Factor ◽  
Polymer Ratio

Aim: Understanding a drug dissolution process from solid dispersions (SD) to develop formulations with predictable in vivo performance. Materials & methods: Dissolution data of fenbendazole released from the SDs and the control physical mixtures were analyzed using the Lumped mathematical model to estimate the parameters of pharmaceutical relevance. Results: The fit data obtained by Lumped model showed that all SDs have a unique dissolution profile with an error of ±4.1% and an initial release rate 500-times higher than the pure drug, without incidence of drug/polymer ratio or polymer type. Conclusion: The Lumped model helped to understand that the main factor influencing the fenbendazole release was the type formulation (SD or physical mixture), regardless of the type or amount of polymer used.

scholarly journals In Vivo Predictive Dissolution Testing of Montelukast Sodium Formulations Administered with Drinks and Soft Foods to Infants

2020 ◽  
Vol 21 (7) ◽  
Author(s):  
J. Martir ◽  
T. Flanagan ◽  
J. Mann ◽  
N. Fotaki
Keyword(s):  
Drug Product ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
Dissolution Testing ◽  
Fed State ◽  
Fasted State ◽  
Direct Administration ◽  
The Impact

Abstract In vitro dissolution testing conditions that reflect and predict in vivo drug product performance are advantageous, especially for the development of paediatric medicines, as clinical testing in this population is hindered by ethical and technical considerations. The aim of this study was to develop an in vivo predictive dissolution test in order to investigate the impact of medicine co-administration with soft food and drinks on the dissolution performance of a poorly soluble compound. Relevant in vitro dissolution conditions simulating the in vivo gastrointestinal environment of infants were used to establish in vitro-in vivo relationships with corresponding in vivo data. Dissolution studies of montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: infant fasted-state simulated gastric fluid (Pi-FaSSGF; for 1 h) followed by either infant fasted-state or infant fed-state simulated intestinal fluid (FaSSIF-V2 or Pi-FeSSIF, respectively; for 3 h). The dosing scenarios tested reflected in vivo paediatric administration practices: (i.) direct administration of formulation; (ii.) formulation co-administered with vehicles (formula, milk or applesauce). Drug dissolution was significantly affected by co-administration of the formulation with vehicles compared with after direct administration of the formulation. Montelukast dissolution from the granules was significantly higher under fed-state simulated intestinal conditions in comparison with the fasted state and was predictive of the in vivo performance when the granules are co-administered with milk. This study supports the potential utility of the in vitro biorelevant dissolution approach proposed to predict in vivo formulation performance after co-administration with vehicles, in the paediatric population.

scholarly journals In Vitro - In Vivo Evaluation Of E/R Trilayer Matrix Tablets Containing Solid Dispersion Of Atorvastatin

2016 ◽  
Vol 8 (3) ◽  
pp. 107
Author(s):  
A Thirupathaiah ◽  
R Shyam Sunder
Keyword(s):  
Extended Release ◽  
Chemical Interaction ◽  
Research Work ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Matrix Tablet ◽  
Dissolution Profile ◽  
Reference Standard

<p>Investigation of <em>in vitro/in vivo</em> behaviour of extended release tablets containing solid dispersions of Atorvastatin is the focus of the present research work. Atorvastatin trilayer matrix tablets were prepared by direct compression method and consisted of middle active layer with different grades of hydroxypropylmethylcellulose (HPMC), ethyl cellulose and Carbopol 934P. Barrier layers are prepared with hydrophobic polymers carnauba wax and xanthan gum. Based on the evaluation parameters, drug dissolution profile and release order kinetics HF16 was found to be optimized formulation. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (HF16) was described by the Zero-order and best fitted to Higuchi model. FTIR confirmed that there was no chemical interaction between drug and excipients used in the formulation. . In vivo bioavailability studies were conducted for optimized formulation HF16 and reference standard. The optimized formulation of Atorvastatin trilayer matrix tablet was shown significant plasma concentration with extended release and maintained for 24 hrs with patient compliance by reducing the dosage frequency, when compared with reference standard. </p>

scholarly journals Exploration of Neusilin® US2 as an Acceptable Filler in HPMC Matrix Systems—Comparison of Pharmacopoeial and Dynamic Biorelevant Dissolution Study

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 127
Author(s):  
Tomáš Bílik ◽  
Jakub Vysloužil ◽  
Martina Naiserová ◽  
Jan Muselík ◽  
Miroslava Pavelková ◽  
...  
Keyword(s):  
Positive Impact ◽  
Drug Dissolution ◽  
Matrix Tablet ◽  
Dissolution Profile ◽  
Dissolution Study ◽  
Biorelevant Dissolution ◽  
Zero Order Kinetics ◽  
Tablet Hardness

Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10–30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices’ evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10–20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms.

Dissolution and Dissolution Test Apparatus: A Review

2021 ◽  
Vol 11 (3) ◽  
pp. 229-236
Author(s):  
Priyanka M. Salve ◽  
Shital V. Sonawane ◽  
Mayuri B. Patil ◽  
Rajendra K. Surawase
Keyword(s):  
Dosage Form ◽  
Immediate Release ◽  
Drug Dissolution ◽  
Dissolution Testing ◽  
Dissolution Test ◽  
Drug Bioavailability ◽  
Drug Degradation ◽  
Chewing Gums ◽  
Dissolution Apparatus

Dissolution is an official test. These used by pharmacopeias for evaluating drug release of solid and semisolid dosages forms. The application of the dissolution testing ensures consistent product quality and to predict in vivo drug bioavailability. The dissolution test, in its simplest form, placing the formulation in a dissolution apparatus containing suitable dissolution medium, allowing it to dissolved specified period of time and then using appropriate rational method to determine the amount of drug. Dissolution test are probative and analysis like drug degradation profile, shelf-life studies, stability, physical and mechanical testing of dosage forms. The present review outlines findings on various dissolution apparatus, various methods and their modification. Dissolution testing the of various dosage form like Delayed release dosage form, Immediate release dosage form, Extended-release dosage form, Powders, Chewable tablets, Transdermal delivery system, Buccal tablets, Soft gelatin capsule, Chewing gums, Suppositories, Aerosols and others semisolids. This article goal of the description of the all-official dissolution testing apparatus.

scholarly journals SYSTEMATIC REVIEW: THE ENHANCEMENT OF ANTI-INFLAMMATION ACTIVITY OF NON STEROIDAL ANTI-INFLAMMATORY DRUG (NSAID) BY SOLID DISPERSION MODIFICATIONS

2021 ◽  
pp. 1-6
Author(s):  
DHEA A. RAMADHANI ◽  
ADI YUGATAMA ◽  
DIAN E. ERMAWATI
Keyword(s):  
Systematic Review ◽  
Solid Dispersion ◽  
The Body ◽  
Inflammatory Activity ◽  
Dissolution Profile ◽  
Inclusion Criteria ◽  
Primary Research ◽  
Dispersion System ◽  
Anti Inflammatory

Objective: NSAIDs are very hydrophobic drugs and have low solubility. This causes the bioavailability of NSAIDs to be low in the body thus affect its anti-inflammatory activity. There has been some primary research proven that solid dispersion can increase the solubility and anti-inflammatory activity of NSAIDs. Moreover, there are not researches explaining the effect of a solid dispersion system on the anti-inflammatory activity of NSAIDs. Therefore, it is necessary to conduct a review to assess the effect of the solid dispersion system on the solubility and anti-inflammatory activity of NSAIDs systematically. Methods: This was systematic review research, where the data were originated from PubMed and Science Direct with the keywords ‘NSAID’, ‘solid dispersion’, and ‘drug effect’. The inclusion criteria formulated were English-language papers, published in 2010–2020, and primary research that conducted in vivo anti-inflammatory testing. The appropriate papers by the inclusion criteria were assessed its quality by the SYRCLE’s tool. Data was analyzed narratively. Results: The results were eight papers under the inclusion criteria. As a whole is known modification of solid dispersion can increase the dissolution profile of NSAIDs. This is because the polymer used can increase the wetting of drug particles, thereby being able to increase the solubility of NSAIDs. Conclusion: The anti-inflammatory activity of NSAIDs by solid dispersion systems are increases compared to NSAIDs without solid dispersions.

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