Development and validation of an intrinsic dissolution method for nimodipine polymorphs

AbstractThe polymorphs of nimodipine, Modification I (Mod I), the metastable racemate, and Modification II (Mod II), the stable conglomerate, were evaluated by means of the intrinsic dissolution procedure. For this purpose, a hydro alcoholic solution (ethanol:water, 50:50, v/v) was selected as the dissolution medium, maintained at 37±0.5°C. Different rotation speeds were tested (50, 75 and 100 rpm) and the lower one was chosen for the test validation. Although the sample initially characterized as polymorph Mod I presented higher intrinsic dissolution rates in all the conditions tested, no statistical differences were noticed between the two polymorphs. This result can be attributed to the partial solution-mediated phase transformation from Mod I to Mod II, detected through X-ray powder diffraction and differential scanning calorimetry. Also, reliable intrinsic dissolution rate data were acquired for the polymorph Mod II. The dissolution method was validated, being considered stable, specific, linear, sensible, accurate and precise.

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Effect of Solid Forms on Physicochemical Properties of Valnemulin

Crystals ◽

10.3390/cryst9120675 ◽

2019 ◽

Vol 9 (12) ◽

pp. 675 ◽

Cited By ~ 2

Author(s):

Jinbo Ouyang ◽

Jian Chen ◽

Limin Zhou ◽

Fangze Han ◽

Xin Huang

Keyword(s):

Organic Acids ◽

Physicochemical Properties ◽

Excess Enthalpy ◽

Vapor Sorption ◽

Dynamic Vapor Sorption ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

X Ray ◽

Ft Ir ◽

Scanning Electron

To improve the physicochemical properties of valnemulin (VLM), different solid forms formed by VLM and organic acids, including tartaric acid (TAR), fumaric acid (FUM), and oxalic acid (OXA), were successfully prepared and characterized by using differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray powder diffraction (XRPD), and Fourier-transform infrared spectroscopy (FT-IR). The excess enthalpy Hex between VLM and other organic acids was calculated by COSMOthermX software and was used to evaluate the probability of forming multi-component solids between VLM and organic acids. By thermal analysis, it was confirmed that multi-component solid forms of VLM were thermodynamically more stable than VLM itself. Through dynamic vapor sorption (DVS) experiments, it was found that three multi-component solid forms of VLM had lower hygroscopicity than VLM itself. Furthermore, the intrinsic dissolution rate of VLM and its multi-component forms was determined in one kind of acidic aqueous medium by using UV-vis spectrometry. It was found that the three multi-component solid forms of VLM dissolved faster than VLM itself.

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Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Pharmaceutics ◽

10.3390/pharmaceutics12030289 ◽

2020 ◽

Vol 12 (3) ◽

pp. 289

Author(s):

Debora Zanolla ◽

Dritan Hasa ◽

Mihails Arhangelskis ◽

Gabriela Schneider-Rauber ◽

Michele R. Chierotti ◽

...

Keyword(s):

Dissolution Rate ◽

Polymorphic Form ◽

In Vitro Tests ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Experimental Conditions ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

X Ray ◽

Enhanced Solubility

Praziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been discovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of multicomponent forms of PZQ a relevant example of a racemic hemihydrate (PZQ-HH), obtainable from commercial PZQ (polymorphic Form A) through mechanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, polarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diffraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed peculiar biopharmaceutical features including enhanced solubility and a double intrinsic dissolution rate in water in comparison to the commercially available PZQ Form A.

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Structures and physicochemical properties of vortioxetine salts

Acta Crystallographica Section B Structural Science Crystal Engineering and Materials ◽

10.1107/s2052520616010556 ◽

2016 ◽

Vol 72 (5) ◽

pp. 723-732 ◽

Cited By ~ 6

Author(s):

Xinbo Zhou ◽

Xiurong Hu ◽

Suxiang Wu ◽

Jiali Ye ◽

Mengying Sun ◽

...

Keyword(s):

Antidepressant Drug ◽

Drug Candidate ◽

X Ray Diffraction ◽

High Solubility ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

X Ray ◽

Acidic Proton ◽

Water Ph ◽

Ft Ir

In the present work, novel salts of the multimodal antidepressant drug vortioxetine (VT) were crystallized with pharmaceutically acceptable acids, aiming to improve the solubility of VT. The acids for VT were selected based on ΔpKabeing greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric acid (HCl),p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid (ASP) were reported. All salts were characterized by single-crystal X-ray diffraction, FT–IR, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The acidic proton is transferred to the secondary N atom on the piperazine ring of VT, forming the charge-assisted hydrogen bond N+—H...X−(X= Cl, Br, O). Solubility and intrinsic dissolution rate (IDR) experiments were carried out in distilled water (pH = 7.0) to compare the solubilities of the salts with that of VT. The VT–ASP–H2O (1:1:2) salt showed 414 times higher solubility and 1722 times faster IDR compared with VT. VT–ASP–H2O (1:1:2) is a high solubility salt that is stable in a slurry experiment at 298 K in 95% ethanol. The experimental data for the VT–ASP–H2O (1:1:2) salt identify it as a promising drug candidate.

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Development and Validation of RP-HPLC Chromatographic Dissolution Method for the Simultaneous Estimation of Ramipril and Hydrochlorothiazide from Solid Dosage Formulation

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i42b32440 ◽

2021 ◽

pp. 203-217

Author(s):

Prabhakar V. Raut ◽

Sudhakar L. Padwal ◽

Madhusudhan T. Bachute ◽

Satish A. Polshettiwar

Keyword(s):

Method Development ◽

Theoretical Plate ◽

Hplc Method ◽

Simultaneous Estimation ◽

Dissolution Medium ◽

Dissolution Method ◽

Rp Hplc ◽

Relative Standard ◽

Limit Of Quantitation ◽

Development And Validation

The present study describes the dissolution method development and validation of Ramipril and Hydrochlorothiazide in tablet dosage form by HPLC Method. A simple, rapid, selective, reproducible and isocratic reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated as per ICH guidelines. Analysis was performed on a Thermo, Sunniest C8 (150 mm x 4.6 mm, 5 µm) with the mobile phase consisting of mixing 500 mL of buffer solution and 500 mL of acetonitrile at a flow rate of 1.0mL/min. UV detection was performed at 210nm and the Run time for Ramipril and Hydrochlorothiazide were 10 minutes. The calibration curve was linear (correlation coefficient = 1.000) in the selected range for both analytes. The optimized dissolution conditions include the USP Type 1 (Basket) rotation rate of 100 rpm and 750 mL of 0.1 N Hydrochloric acid as dissolution medium, at 37.0 ± 0.5°C. The method was validated for precision, linearity, specificity, accuracy, limit of quantitation and ruggedness. The system suitability parameters, such as theoretical plate, tailing factor and relative standard deviation (RSD) between six standard replicates were well within the limits. The stability result shows that the drug is stable in the prescribed dissolution medium.

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DISSOLUTION METHOD DEVELOPMENT AND VALIDATION OF TRAMADOL HYDROCHLORIDE CAPSULES

INDIAN DRUGS ◽

10.53879/id.50.08.p0047 ◽

2013 ◽

Vol 50 (08) ◽

pp. 47-50

Author(s):

H Farheen ◽

◽

T Mamatha . ◽

Z Yasmeen ◽

Rao J. Venkateswara

Keyword(s):

Method Development ◽

Estimation Method ◽

Dissolution Behavior ◽

Official Method ◽

Dissolution Medium ◽

Tramadol Hydrochloride ◽

Dissolution Method ◽

Ich Guidelines ◽

Development And Validation ◽

Usp Apparatus

A dissolution method was developed and validated for evaluation of the dissolution behavior of capsule dosage form of tramadol hydrochloride as there was no official method available. The UV spectrophotometric method developed was based on the direct estimation method using 271 nm as λmax of tramadol hydrochloride. The method was validated according to International Conference on Harmonisation (ICH) guidelines which include accuracy, precision, specificity, linearity, and analytical range. In addition, solubility and stability of the drug in dissolution medium i.e., 0.1 N HCl was studied. The established dissolution conditions were 900 mL dissolution medium at temperature 37 ± 0.5°C, using USP apparatus I at stirring rate of 100 rpm for 30 min. The corresponding dissolution profiles were constructed and all the selected brands showed more than 80% drug release with in 30 min. Thus, the proposed dissolution method can be applied successfully for the quality control of tramadol hydrochloride capsules.

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Triamterene–furosemide salt: structural aspects and physicochemical evaluation

Acta Crystallographica Section B Structural Science Crystal Engineering and Materials ◽

10.1107/s2052520618013185 ◽

2018 ◽

Vol 74 (6) ◽

pp. 738-741 ◽

Cited By ~ 4

Author(s):

Bo Peng ◽

Jian-Rong Wang ◽

Xuefeng Mei

Keyword(s):

Alternative Formulation ◽

Valuable Insight ◽

Dynamic Vapor Sorption ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

X Ray ◽

Poor Solubility ◽

Physicochemical Evaluation ◽

Potential Alternative ◽

Novel Drug

Furosemide (Fur) is a BCS class IV diuretic drug with low bioavailability due to its poor solubility and poor membrane permeability. Triamterene (Tri) is a potassium-sparing diuretic with low bioavailability due to its poor solubility. Here, a novel drug–drug salt composed of Tri and Fur was successfully synthesized. Tri–Fur was comprehensively characterized with single-crystal X-ray and powder X-ray diffraction techniques, thermogravimetric analysis, differential scanning calorimetry and dynamic vapor sorption. The apparent equilibrium solubility (in pH 2.0 buffer) of Tri–Fur is improved compared with Fur and a physical mixture of Tri with equimolar Fur by 15.3-fold and 12.2-fold enhancements, respectively. Its intrinsic dissolution rate (in pH 2.0 buffer) is also higher than for a Fur component with an enhancement of 9.5-fold. This study provides a valuable insight into the formation of dual pharmaceutical salts and demonstrates that Tri–Fur can be a potential alternative formulation.

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PARTIAL AMORPHIZATION OF POORLY-SOLUBLE SIMVASTATIN USP USING MEDIA MILLING IN SYNERGISM WITH SPRAY-DRYING

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2020v12i11.39373 ◽

2020 ◽

pp. 114-121

Author(s):

HARITA R. DESAI ◽

ARCHANA B. RAJADHYAX ◽

PURNIMA D. AMIN

Keyword(s):

Differential Scanning Calorimetry ◽

Spray Drying ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

X Ray ◽

Media Milling ◽

Rate Testing ◽

Poorly Soluble ◽

Spray Dried

Objective: The objective of the current study was to explore top down methods of size reduction like high speed homogenisation and media milling in synergism with spray drying in amorphization and solubility enhancement of BCS Class II antilipidemic drug Simvastatin USP. Methods: Spray-dried micronized simvastatin USP was formulated by homogenisation and media milling of drug suspension in optimized stabilizer solution. Stabilizer combination, duration of homogenisation and ball milling and drug: stabilizer ratio was optimized. The obtained dispersion was transformed into solid powder using spray drying. The obtained Spray-dried micronized Simvastatin USP was evaluated for visual morphology, Infrared spectroscopy, Differential scanning calorimetry, in vitro drug release studies, X-Ray diffractometry, Scanning electron microscopy, contact angle measurement, solubility studies, dispersibility studies and intrinsic dissolution rate testing. Results: Spray-dried micronized simvastatin USP was found to show amorphization of crystalline Simvastatin USP as confirmed by the absence of drug peak in Differential scanning calorimetry and lowered signal intensity in X-Ray diffraction studies. Spray-dried micronized Simvastatin USP was found to show enhanced drug hydrophilicity and solubility as confirmed by lowering in contact angle and increase in solubility and ease of dispersibility observations. In vitro dissolution testing and intrinsic dissolution rate testing were found to show an increase in drug release from 11% to 79% and 4 mg min-1 cm-2 to 17 mg min-1 cm-2 for drug and Spray-dried micronized Simvastatin USP respectively. Conclusion: Media milling in synergism with spray-drying was found to be a prospective solubility enhancement technique for poorly-soluble Simvastatin USP.

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Improving the Solubility of Aripiprazole by Multicomponent Crystallization

Crystals ◽

10.3390/cryst11040343 ◽

2021 ◽

Vol 11 (4) ◽

pp. 343

Author(s):

Qi Zhou ◽

Zhongchuan Tan ◽

Desen Yang ◽

Jiyuan Tu ◽

Yezi Wang ◽

...

Keyword(s):

Dissolution Rate ◽

Weak Interactions ◽

Theoretical Calculations ◽

Water Soluble ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

X Ray ◽

Water Soluble Drugs

Aripiprazole (ARI) is a third-generation antipsychotic with few side effects but a poor solubility. Salt formation, as one common form of multicomponent crystals, is an effective strategy to improve pharmacokinetic profiles. In this work, a new ARI salt with adipic acid (ADI) and its acetone hemisolvate were obtained successfully, along with a known ARI salt with salicylic acid (SAL). Their comprehensive characterizations were conducted using X-ray diffraction and differential scanning calorimetry. The crystal structures of the ARI-ADI salt acetone hemisolvate and ARI-SAL salt were elucidated by single-crystal X-ray diffraction for the first time, demonstrating the proton transfer from a carboxyl group of acid to ARI piperazine. Theoretical calculations were also performed on weak interactions. Moreover, comparative studies on pharmaceutical properties, including powder hygroscopicity, stability, solubility, and the intrinsic dissolution rate, were carried out. The results indicated that the solubility and intrinsic dissolution rate of the ARI-ADI salt and its acetone hemisolvate significantly improved, clearly outperforming that of the ARI-SAL salt and the untreated ARI. The study presented one potential alternative salt of aripiprazole and provided a potential strategy to increase the solubility of poorly water-soluble drugs.

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Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate

Pharmaceutics ◽

10.3390/pharmaceutics14010023 ◽

2021 ◽

Vol 14 (1) ◽

pp. 23

Author(s):

Chenxin Duan ◽

Wenwen Liu ◽

Yunwen Tao ◽

Feifei Liang ◽

Yanming Chen ◽

...

Keyword(s):

Water Solubility ◽

Cancer Drug ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Dissolution Rates ◽

Intrinsic Dissolution ◽

X Ray ◽

Enhanced Solubility

Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC50 value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics.

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Dissolution Method Development and Validation for Estimation of Noscapine Tablets

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i1-s.3891 ◽

2020 ◽

Vol 10 (1-s) ◽

pp. 159-164

Author(s):

Jigar Vyas ◽

Jaydip Solanaki ◽

Kapil Daxini ◽

Puja Vyas ◽

Neha Pal

Keyword(s):

Method Development ◽

Uv Spectrophotometry ◽

Dissolution Test ◽

Dissolution Medium ◽

Dissolution Method ◽

Method Development And Validation ◽

Development And Validation ◽

Usp Apparatus ◽

Usp Apparatus 2

A dissolution method was developed and UV spectrophotometry was developed for the evaluation of the dissolution of tablets containing 15 mg Noscapine .The dissolution medium 0.1 N HCl was found suitable to ensure sink conditions. USP Apparatus 2, 900 mL dissolution medium 45 minutes and 100 RPM were fixed. Dissolution profiles were generated at 10, 15, 20, 30; 45 min. Dissolution samples were analyzed with UV spectrophotometer at 213 nm. The UV method for determination of tablet was developed and validated. The method presented linearity (R2 = 0.999) in the concentration range of 1–9 μg/mL. The recoveries were good, ranging from 97.18% to 101.45%. The intraday and Interday precision results were 0.54% and 0.78% RSD, respectively. The developed dissolution test is adequate for its purpose and can be applied for the quality control of tablets. Keywords: Dissolution test; Noscapine; Tablets; UV Spectrophotometry method

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