Optimally Predictive In Vitro Drug Dissolution Testing for In Vitro Bioavailability

Abstract Paediatric medicines are not always age-appropriate, causing problems with dosing, acceptability and adherence. The use of food and drinks as vehicles for medicine co-administration is common practice, yet the impact on drug bioavailability, safety and efficacy remains unaddressed. The aim of this study was to use in vitro dissolution testing, under infant simulating conditions, to evaluate the effect of co-administration with vehicles on the dissolution performance of two poorly soluble paediatric drugs. Dissolution studies of mesalazine and montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: simulated gastric fluid followed by addition of simulated intestinal fluid. The testing scenarios were designed to reflect daily administration practices: direct administration of formulation; formulation co-administered with food and drinks, both immediately after mixing and 4 h after mixing. Drug dissolution was significantly affected by medicine co-administration with vehicles, compared to the direct administration of formulation. Furthermore, differences were observed on drug dissolution when the formulations were mixed with different vehicles of the same subtype. The time between preparation and testing of the drug-vehicle mixture also impacted dissolution behaviour. Drug dissolution was shown to be significantly affected by the physicochemical properties and composition of the vehicles, drug solubility in each vehicle and drug/formulation characteristics. Ultimately, in this study, we show the potential of age-appropriate in vitro dissolution testing as a useful biopharmaceutical tool for estimating drug dissolution in conditions relevant to the paediatric population. The setup developed has potential to evaluate the impact of medicine co-administration with vehicles on paediatric formulation performance.

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

AAPS PharmSciTech ◽

10.1208/s12249-020-01825-7 ◽

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.

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In-Vitro Drug Dissolution Studies in Medicinal Compounds

Current Medicinal Chemistry ◽

10.2174/0929867325666180322145335 ◽

2018 ◽

Vol 25 (33) ◽

pp. 4020-4036

Author(s):

Burcin Bozal-Palabiyik ◽

Bengi Uslu ◽

Yalcin Ozkan ◽

Sibel A. Ozkan

Keyword(s):

Dosage Form ◽

Dosage Forms ◽

Drug Dissolution ◽

Dissolution Testing ◽

Solid Dosage Forms ◽

Solid Dosage ◽

The Media ◽

Recent Trends ◽

Selection Of

After oral administration, drug absorption from solid dosage forms depends on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover, dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained.

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Formulation Development and Characterization of controlled release core in cup matrix tablets of venlafaxine HCl

Current Drug Therapy ◽

10.2174/1574885515666200331104440 ◽

2020 ◽

Vol 15 ◽

Author(s):

Balaji Maddiboyina ◽

Vikas Jhawat ◽

Gandhi Sivaraman ◽

Om Prakash Sunnapu ◽

Ramya Krishna Nakkala ◽

...

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Zero Order ◽

Water Soluble ◽

Matrix Tablets ◽

Drug Dissolution ◽

Crystalline Cellulose ◽

Hydrophobic Polymers

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl were prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium sterate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification, In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson–crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in acceptable range for all formulations. Based on the In vitro dissolution profile, formulation F-9 was considered to be the optimized extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and also compared with innovator product (flavix XR) showed better drug release profile. Conclusion: The core-in-cup technology has a potential to control the release rate of freely water soluble drugs for single administration per day by optimization with combined use of hydrophilic and hydrophobic polymers.

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In vitro dissolution testing models of ocular implants for posterior segment drug delivery

Drug Delivery and Translational Research ◽

10.1007/s13346-021-01043-z ◽

2021 ◽

Author(s):

Muhammad Faris Adrianto ◽

Febri Annuryanti ◽

Clive G. Wilson ◽

Ravi Sheshala ◽

Raghu Raj Singh Thakur

Keyword(s):

Drug Release ◽

Posterior Segment ◽

In Vitro Dissolution ◽

Prolonged Treatment ◽

Term Therapy ◽

In Vitro Test ◽

Dissolution Testing ◽

Vitro Test ◽

Ocular Implants

AbstractThe delivery of drugs to the posterior segment of the eye remains a tremendously difficult task. Prolonged treatment in conventional intravitreal therapy requires injections that are administered frequently due to the rapid clearance of the drug molecules. As an alternative, intraocular implants can offer drug release for long-term therapy. However, one of the several challenges in developing intraocular implants is selecting an appropriate in vitro dissolution testing model. In order to determine the efficacy of ocular implants in drug release, multiple in vitro test models were emerging. While these in vitro models may be used to analyse drug release profiles, the findings may not predict in vivo retinal drug exposure as this is influenced by metabolic and physiological factors. This review considers various types of in vitro test methods used to test drug release of ocular implants. Importantly, it discusses the challenges and factors that must be considered in the development and testing of the implants in an in vitro setup. Graphical abstract

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Dissolution Testing of Nicotine Release from OTDN Pouches: Product Characterization and Product-to-Product Comparison

Separations ◽

10.3390/separations8010007 ◽

2021 ◽

Vol 8 (1) ◽

pp. 7

Author(s):

Fadi Aldeek ◽

Nicholas McCutcheon ◽

Cameron Smith ◽

John H. Miller ◽

Timothy L. Danielson

Keyword(s):

In Vitro Release ◽

Product Category ◽

Immediate Release ◽

Tobacco Product ◽

Oral Dosage ◽

Dissolution Testing ◽

Release Rates ◽

Usp 4 ◽

Release Profiles

In recent years, oral tobacco-derived nicotine (OTDN) pouches have emerged as a new oral tobacco product category. They are available in a variety of flavors and do not contain cut or ground tobacco leaf. The on!® nicotine pouches fall within this category of OTDN products and are currently marketed in seven (7) flavors with five (5) different nicotine levels. Evaluation of the nicotine release from these products is valuable for product assessment and product-to-product comparisons. In this work, we characterized the in vitro release profiles of nicotine from the 35 varieties of on!® nicotine pouches using a fit-for-purpose dissolution method, employing the U.S. Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4). The nicotine release profiles were compared using the FDA’s Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms. The cumulative release profiles of nicotine show a dose dependent response for all nicotine levels. The on!® nicotine pouches exhibit equivalent percent nicotine release rates for each flavor variant across all nicotine levels. Furthermore, the nicotine release profiles from on!® nicotine pouches were compared to a variety of other commercially available OTDN pouches and traditional pouched smokeless tobacco products. The percent nicotine release rates were found to be dependent on the product characteristics, showing similarities and differences in the nicotine release profiles between the on!® nicotine pouches and other compared products.

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

Scientific Reports ◽

10.1038/s41598-019-53750-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

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.

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DESIGN, OPTIMIZATION AND EVALUATION OF CETRIZINE DIHYDROCHLORIDE FAST DISSOLVING FILMS EMPLOYING STARCH TARTRATE–A NOVEL SUPERDISINTEGRANT

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2019v11i6.36347 ◽

2019 ◽

pp. 75-86

Author(s):

R. SANTOSH KUMAR ◽

ANNU KUMARI ◽

B. KUSUMA LATHA ◽

PRUDHVI RAJ

Keyword(s):

Tensile Strength ◽

Drug Dissolution ◽

In Vitro Dissolution ◽

Content Uniformity ◽

Scanning Calorimetry ◽

Disintegration Time ◽

Folding Endurance ◽

Contour Plots ◽

The Individual

Objective: The aim of the current research is optimization, preparation and evaluation of starch tartrate (novel super disintegrant) and preparation of fast dissolving oral films of cetirizine dihydrochloride by employing starch tartrate. Methods: To check the drug excipient compatibility studies of the selected drug (Cetrizine dihydrochloride) and the prepared excipient i. e starch tartrate, different studies like FTIR (Fourier-transform infrared spectroscopy), DSC (Differential scanning calorimetry) and thin-layer chromatography (TLC) were carried out to find out whether there is any interaction between cetirizine dihydrochloride and starch tartrate. The solvent casting method was used for the preparation of fast dissolving films. The prepared films were then evaluated for thickness, folding endurance, content uniformity, tensile strength, percent elongation, in vitro disintegration time and in-vitro dissolution studies. Response surface plots and contour plots were also plotted to know the individual and combined effect of starch tartrate (A), croscarmellose sodium (B) and crospovidone (C) on disintegration time and drug dissolution efficiency in 10 min (dependent variables). Results: Films of all the formulations are of good quality, smooth and elegant by appearance. Drug content (100±5%), thickness (0.059 mm to 0.061 mm), the weight of films varies from 51.33 to 58.06 mg, folding endurance (52 to 67 times), tensile strength (10.25 to 12.08 N/mm2). Fast dissolving films were found to disintegrate between 34 to 69 sec. Percent dissolved in 5 min were found to be more in F1 formulation which confirms that starch tartrate was effective at 1%. Conclusion: From the research conducted, it was proved that starch tartrate can be used in the formulation of fast dissolving films of cetirizine dihydrochloride. The disintegration time of the films was increased with increase in concentration of super disintegrant.

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