Modulation of pH-Independent Release of a Class ΙΙ Drug (Domperidone) from a Polymeric Matrix Using Acidic Excipients

Khan, Amjad; Iqbal, Zafar; Khan, Abad; Mughal, Muhammad Akhlaq; Khan, Abbas; Ullah, Zia; Khan, Ismail

doi:10.14227/dt230116p32

Cited by 8 publications

(8 citation statements)

References 12 publications

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“…This behavior of CA is attributed to the high capacity of hydrogen bond formation with the polymer, confirmed by several reports [5][6][7]. Also, CA is a microenvironmental pH acidifier that helps to provide the desired drug release rate in any environmental pH [8,9]. Herein, we propose to develop SD using a thermoplastic polymer, Eudragit EPO, and a solid-state plasticizer, CA.…”

Section: Introductionsupporting

confidence: 53%

RP-HPLC method development and validation for the quantification of Efonidipine hydrochloride in HME processed solid dispersions

et al. 2020

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Background Efonidipine hydrochloride (EFO) is a poorly water-soluble drug and, hence, has poor bioavailability. Solid dispersions (SDs) of EFO using Eudragit EPO were prepared using hot-melt extrusion (HME) for the first time. The current study aims at developing a simple RP-HPLC method to quantify EFO in the developed SDs. Results The chromatographic separation was carried out on an Agilent Eclipsed XDB-C18 column (4.6 × 250 mm), packed with 5 μm particles. The optimized mobile phase consisted of HPLC grade acetonitrile and 0.020 mol/L KH2PO4 (pH 2.5) buffer in the ratio of 85:15 v/v with a flow rate optimized at 1.2 ml/min. The developed method was validated for system suitability, linearity, accuracy, precision, and robustness. The linearity results showed an excellent linear relationship between the drug concentration and peak area, indicating the peak area is directly proportional to the analyte concentration within a specific range and an excellent correlation coefficient of 0.9998. Intermediate precision and repeatability confirmed that the method provides precise results with %RSD value less than 2% for EFO. The assay results of the developed formulations were in the acceptable range with RSD less than 2%. The enhanced drug dissolution from the Eudragit EPO carrier with 10% Citric Acid (CA) is attributed to the conversion of the drug from crystalline to amorphous form, and microenvironmental acidic pH provided by CA. Conclusion In a nutshell, the developed RP-HPLC method showed excellent ability to differentiate the formulations and highlights the role of the polymer and the plasticizer. Graphical abstract

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Section: Introductionsupporting

confidence: 53%

RP-HPLC method development and validation for the quantification of Efonidipine hydrochloride in HME processed solid dispersions

et al. 2020

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“…Dissimilarity factor (f 1 ) was calculated using the Equation3 and similarity factor (f 2 ) was calculated using Equation 4. 18,19 [ ] 1 1 00…”

Section: Comparison Of In-vitro Drug Release Profile Of Marketed Tablmentioning

confidence: 99%

“…Aqueous solubility and permeability of any active Pharmaceutical ingredient are the key properties as these govern dissolution rate and subsequent absorption from gastro intestinal tract. 1 Most of the newly invented APIs are hydrophobic in nature having poor water solubility and good permeability i.e. when released from the dosage form is rapidly absorbed.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of co‒grinding on dissolution rate of poor water soluble drug (clarithromycin)

Iqbal

Khan

Niaz

2018

MOJDDT

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Most of the newly invented active pharmaceutical ingredients (APIs) are poor water soluble and dissolution rate is the limiting step in bioavailability from compressed solid dosage forms. Objective of the study was to elucidate the effect of hydrophilic carriers on dissolution rate of poor water soluble drug and utilization of co-grinded Clarithromycin in preparation of tablets by direct compression. Intrinsic dissolution rate of Clarithromycin was determined according to United States Pharmacopeia (USP) using rotating disk method. Hydrophilic carrier (micro crystalline cellulose) was applied in varying ratios (1:1, 1:2 and 1:4; drug to carrier ratio by weight) for enhancement of dissolution rate of Clarithromycin by co-grinding technique. Co-grinded Clarithromycin was prepared by compressing lubricated physical mixture (blend of Clarithromycin and micro crystalline cellulose) to slugs, followed by granulation. Tablets containing co-grinded Clarithromycin were prepared by direct compression technique and evaluated for various official and unofficial parameters at pre compression and post compression level. The prepared tablets were compared with marketed tablets in terms of physical parameters, mechanical strength, disintegration behavior and in-vitro drug release. Dissolution profiles of both types of the tablets were compared on the basis of maximum drug release, dissimilarity factor (f 1), similarity factor (f 2) and dissolution efficiency. Clarithromycin is a class-II drug, with poor water solubility. Its intrinsic dissolution rate is very low (0.678mg/cm 2 .min). In comparison to intrinsic dissolution rate, significant increase in dissolution rate of Clarithromycin was observed by co-grinding with hydrophilic carriers (267.11%). Dissolution rate of Clarithromycin enhanced with concentration of hydrophilic carrier and maximum increase was observed at 1:2 (drug to carrier ratio by weight). By further increasing ratio of the carrier resulted in decrease in dissolution rate due to cushioning effect. Tablets containing cogrinded Clarithromycin, showed better dissolution profile compared with marketed tablets. In comparison with marketed tablets, maximum drug release in 60min, Q60 (99.73±0.39), Q30 (75.81±0.19%), Q15 (31.17±0.26%), and dissolution efficiency (93.73%) were higher for tablets containing co-grinded Clarithromycin. Dissolution rate of poor water soluble drug (Clarithromycin) can be enhanced by co-grinding with hydrophilic carrier (micro crystalline cellulose). Co-grinding is an environment friendly technique that can be applied for enhancement of dissolution rate of poor water soluble APIs irrespective of nature and dose.

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“…During granulation, PVP forms strong bonds among the particles, holding them strongly and increases the inherent strength of the granules (20). Furthermore, PVP is a hydrophilic polymer which swells upon contact with water, forming a gel layer to control the drug release (21). When used in higher concentration, it forms a thick gel layer and retards drug release.…”

Section: Dissolution Testing Of the Processed Granulesmentioning

confidence: 99%

Intrinsic dissolution testing: A tool for determining the effect of processing on dissolution behavior of the drug

Khan¹,

Iqbal²,

Khan³

et al. 2017

Dissolution Technol.

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Intrinsic dissolution testing has been applied for characterization of pure API with respect to its dissolution behavior. The effect of formulation factors and processing parameters on dissolution rate is evaluated by dissolution testing of the final product, which is a time and resource-consuming process. Our objective was to use intrinsic dissolution testing for determining the effect of processing parameters on drug release. In the present study, an intrinsic dissolution testing method was developed for atenolol and validated according to the standard guidelines using USP-recommended dissolution media. Various experimental variables (compaction pressure and rotation speed of the disk) were optimized by studying at three levels. Atenolol was subjected to granulation in a super mixer granulator by applying standard wet granulation protocols. Granulation time and binder concentration were taken as process variables while dissolution rate was a response variable. Dissolution media had no interference with sample analysis, and all validation parameters for the developed method were in an acceptable range (%RSD > 1). The intrinsic dissolution rate of atenolol (1.84 ± 0.13 mg/cm 2 min) was high due to its better solubility in dissolution media. The dissolution rate of atenolol was decreased by granulating with PVP under different conditions. We concluded that intrinsic dissolution testing method can be applied for determining the effect of processing parameters on dissolution rate of the API at the pre-compression level. This method will reduce experimentation for optimization of dissolution rate and will spare time and resources.

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Modulation of pH-Independent Release of a Class ΙΙ Drug (Domperidone) from a Polymeric Matrix Using Acidic Excipients

Cited by 8 publications

References 12 publications

RP-HPLC method development and validation for the quantification of Efonidipine hydrochloride in HME processed solid dispersions

RP-HPLC method development and validation for the quantification of Efonidipine hydrochloride in HME processed solid dispersions

Evaluation of the effect of co‒grinding on dissolution rate of poor water soluble drug (clarithromycin)

Intrinsic dissolution testing: A tool for determining the effect of processing on dissolution behavior of the drug

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