Developing Discriminatory Drug Dissolution Tests and Profiles: Some Thoughts for Consideration on the Concept and Its Interpretation

Qureshi, Saeed A.

doi:10.14227/dt130406p18

Cited by 30 publications

(17 citation statements)

References 16 publications

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“…Drug release of a poorly soluble drug like EFV, as used in the study, is usually driven more by the medium than by the formulation ingredients. Discriminatory dissolution profiles are highly desirable for distinguishing between products showing differences in pharmaceutical attributes (formulation or manufacturing process differences) as is the case in the present study, wherein the difference in formulation was only with respect to the disintegrant used (10)(11)(12)(13). Figure 1 shows the dissolution profile of 600-mg EFV tablet in water containing different concentrations of SLS containing CP as disintegrant.…”

Section: In Vitro Dissolution Studiesmentioning

confidence: 88%

Impact of superdisintegrants on efavirenz release from tablet formulations

Yelchuri

Balasubramaniam

K³

et al. 2010

Acta Pharmaceutica

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EFV is a non-nucleoside reverse transcriptase inhibitor and is used as part of the highly active antiretroviral therapy for the treatment of human immunodeficiency virus type 1 (HIV) infection. It is also used in combination with other antiretroviral agents as part of an expanded post-exposure prophylaxis regimen to prevent HIV transmission for those exposed to materials associated with a high risk of HIV transmission.EFV has poor aqueous solubility and is a BCS class II drug (1). EFV tablets of 600 mg are available, while lower doses (50, 100 and 200 mg) are generally available as capsules and are prepared by a wet granulation process (2, 3). 185Acta Pharm. 60 (2010) [185][186][187][188][189][190][191][192][193][194][195] Original research paper DOI: 10.2478/v10007-010-0019-6 Impact of superdisintegrants on efavirenz release from tablet formulations Efavirenz (EFV) tablets of different doses were prepared by a wet granulation process using different superdisintegrants such as crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crosspovidone (CP) to evaluate the role of different disintegrants on the in vitro release of EFV. Further, the mode of addition of disintegrants on EFV dissolution from tablets containing 600 mg of the drug was evaluated by incorporating the disintegrants extragranularly (EG), intragranularly (IG) or distributing them equally (IG and EG). In vitro dissolution of the prepared tablets was conducted using the recommended medium and a dissolution medium developed in-house, which had the ability to discriminate between the formulations.The t 50 and t 80 values were indicative of the fact that the drug release was faster from tablet formulations containing CP. CP was able to release the drug faster than the other two disintegrants in both dissolution media and the drug release was unaffected by the mode of CP addition.Keywords: efavirenz, superdisintegrants, granulation * Correspondence; e-mail: rajeshyelchuri@rediffmail.com Brought to you by | MIT Libraries Authenticated Download Date | 5/12/18 2:48 PM Superdisintegrants generally improve disintegration efficiency compared to traditional disintegrants. They are generally used at low levels in solid dosage forms, typically 1-10 % of mass relative to the total mass of the dosage unit (4). Examples of superdisintegrants are crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crosspovidone (CP), which are cross-linked cellulose, a cross-linked starch and a cross--linked polymer (polyvinyl pyrrolidone), respectively. Wet granulation is one of the frequently used techniques to prepare blends to be compressed into tablets. The disintegrant can be incorporated in the blend before granulation, referred to as intragranular addition (IG), or after granulation, referred to as extragranular addition (EG), or it can be distributed both intra and extragranularly. EXPERIMENTAL MaterialsEfavirenz (Aurbindo Pharma Ltd., India) was purchased from the source indicated. Crosscarmellose sodium (Ac-di-sol ® , FMC biopolymer) and SS...

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Section: In Vitro Dissolution Studiesmentioning

confidence: 88%

Impact of superdisintegrants on efavirenz release from tablet formulations

Yelchuri

Balasubramaniam

K³

et al. 2010

Acta Pharmaceutica

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“…Solubility of aspirin in water decreased with inclusion of surfactant, which may due to increase in pH. At higher pH, aspirin shows hydrolysis, resulting in reduced solubility and subsequent dissolution rate (26).…”

Section: Selection Of Dissolution Mediamentioning

confidence: 99%

Dissolution testing of bilayer tablets: Method development, validation and application in post-marketing quality evaluation

Khan¹,

Iqbal²

2017

Dissolution Technol.

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Bilayer tablets are gaining importance as they provide a multilayer system for administration of incompatible or synergistic drugs and reduce the dosing unit burden. Furthermore, two different APIs or portions of an API with different release characteristics can be formulated as single unit, having different layers. Most of the research is directed towards physical stability (prevention of delamination), and simultaneous dissolution testing of different APIs in bilayer tablets has been neglected. In the present study, a method was developed for simultaneous determination of dissolution rates of clopidogrel and aspirin from bilayer tablets. Dissolution media was selected on the basis of sink conditions for both the drugs. Various experimental conditions (type of apparatus, agitation rate, and volume of dissolution media) were optimized, and the developed method was validated according to USP and ICH guidelines. Analysis of dissolution samples was carried out by HPLC using an ODS C-18 column (250 x 4.6 mm, 5 μm) as the stationary phase. The mobile phase consisted of a combination of acetonitrile, methanol, and phosphate buffer (50:7:43, v/v/v) pumped at flow rate of 2 mL/min at ambient temperature while the detector wavelength was set at 240 nm. An independent model approach was applied for comparison of dissolution profiles. The best in vitro dissolution profiles were obtained using 900 mL of hydrochloric acid (HCl) buffer (pH 3) as dissolution media held at 37 ± 2°C and stirred at 75 rpm using apparatus-II. Complete dissolution was achieved within 45 min. for both the drugs. Validation parameters revealed accuracy, precision, and robustness of the method without any interference with sample analysis. The developed method will be helpful in dissolution testing of bilayer tablets containing clopidogrel and aspirin at the level of product development and during routine quality control analysis and post-marketing surveillance studies.

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“…Sink conditions occurs when the amount of drug that can be dissolved in the dissolution medium is three times greater than the amount of drug to be dissolved (32). A low C s /C d ratio shows the existence of non-sink conditions with a subsequent lower dissolution rate.…”

Section: Equilibrium Solubility Of Domperidonementioning

confidence: 99%

Development and Validation of a Discriminatory Dissolution Testing Method for Orally Disintegrating Tablets (ODTs) of Domperidone

Khan¹

2017

Dissolution Technol.

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• Disintegration controlled absorption: The APIs have better solubility profiles, and the resultant dosage forms show higher dissolution rates. Dissolution rate of a drug can be enhanced by increasing its disintegration. Development and Validation of a Discriminatory Dissolution Testing Method for Orally Disintegrating Tablets (ODTs) of Domperidone Amjad KhanDepartment of Pharmacy, Abasyn University, Peshawar-25120, Pakistan ABSTRACTThe orally disintegrating tablet (ODT) is a novel dosage form that disintegrates in the oral cavity using saliva as the disintegrating medium and is swallowed as a fine dispersion. Due to rapid disintegration, the dissolution rate is controlled by the intrinsic solubility of the API; therefore, it is difficult to evaluate the effect of formulation and processing parameters on in vitro drug release. Thus, a dissolution method that can discriminate among in vitro release profiles of ODTs with varying natures is needed. The objective of the present study was to develop and validate a discriminative dissolution testing method for ODTs of domperidone. Different experimental conditions such as dissolution medium composition, dissolution medium volume, and paddle rotation speed were evaluated. Analysis of dissolution samples was carried out by HPLC using a combination of water at pH 3 and acetonitrile (65:35 v/v) as the mobile phase. The developed dissolution method was validated according to ICH guidelines for various parameters such as specificity, accuracy, precision, and stability. The discriminatory nature of the method was confirmed by determining the dissolution rate of ODTs containing pulverized and unpulverized domperidone. The best in vitro dissolution profile was obtained using purified water containing 1% Tween 80 as the dissolution medium (900 mL) stirred at 50 rpm. Complete dissolution (100.09 ± 0.37%) was achieved within 60 min, and the dissolution medium did not interfere with sample analysis. All the validation parameters were in an acceptable range (RSD > 2%). A comparison of the dissolution profiles in official and developed media showed significant differences based on f 1 and f 2 values. The developed dissolution test exhibited a higher capacity than the compendial methods in differentiating the release profiles of ODTs. It can be applied during formulation development and quality control analysis of ODTs for evaluation of the effects of formulation and processing parameters.

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Developing Discriminatory Drug Dissolution Tests and Profiles: Some Thoughts for Consideration on the Concept and Its Interpretation

Cited by 30 publications

References 16 publications

Impact of superdisintegrants on efavirenz release from tablet formulations

Impact of superdisintegrants on efavirenz release from tablet formulations

Dissolution testing of bilayer tablets: Method development, validation and application in post-marketing quality evaluation

Development and Validation of a Discriminatory Dissolution Testing Method for Orally Disintegrating Tablets (ODTs) of Domperidone

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