Study of the Impact of Different Salts on the Intrinsic Dissolution Rate of Pharmaceutical Compounds

The intrinsic dissolution rate (IDR) of active pharmaceutical ingredients (API) is a key property that aids in early drug development, especially selecting formulation strategies to improve dissolution and thereby drug absorption in the intestine. Here, we developed a robust method for rapid, medium throughput screening of IDR and established the largest IDR dataset in open literature to date that can be used for pharmaceutical computational modeling. Eighteen compounds with diverse physicochemical properties were studied in both fasted and fed state simulated intestinal fluids. Dissolution profiles were measured in small-scale experimental assays using compound suspensions or discs. IDR measurements were not solely linked to API solubility in either dissolution media. Multivariate data analysis revealed that IDR strongly depends on compound partitioning into bile salt and phospholipid micelles in the simulated intestinal fluids, a process that in turn is governed by API lipophilicity, hydrophobicity, and ionization.

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CHARACTERIZATION AND INTRINSIC DISSOLUTION RATE STUDY OF MICROWAVE ASSISTED CYCLODEXTRIN INCLUSION COMPLEXES OF GEMFIBROZIL

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i10.13359 ◽

2016 ◽

Vol 8 (10) ◽

pp. 160

Author(s):

S. Ain ◽

R. Singh ◽

Q. Ain

Keyword(s):

Inclusion Complex ◽

Dissolution Rate ◽

Inclusion Complexes ◽

Microwave Drying ◽

Phase Solubility ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

Solubility Study ◽

Microwave Assisted ◽

Rate Study

Objective: The aim of the present study was to carry out characterization and intrinsic dissolution rate study of microwave assisted inclusion complex of poorly water soluble, lipid lowering agent gemfibrozil [5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid] with naturally occurring β-cyclodextrins (CDs) or cycloheptaamylase.Methods: In this work, the phase solubility study was performed to find the ratio of drug and cyclodextrin complexes. Inclusion complexes were prepared by kneading and the prepared complex was subjected to microwave drying and conventional drying techniques. The prepared complexes were evaluated by intrinsic dissolution rate studies and equilibrium solubility study. Further characterization was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (DSC).Results: The phase solubility studies showed a linear AL-type diagram indicating the formation of inclusion complexes in 1:1 molar ratio β-CD-gemfibrozil complex with maximum stability constant of 148.88 M-1was selected for preparation of inclusion complex. The microwave dried product was identified as the inclusion complex with maximum IDR when compared to the conventional dried product.Conclusion: This study was concluded that the microwave drying is the most suitable of the previously occurring drying techniques. Since it showed the highest solubility and IDR value.

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Discovery, Characterization, and Pharmaceutical Applications of Two Loratadine–Oxalic Acid Cocrystals

Crystals ◽

10.3390/cryst10110996 ◽

2020 ◽

Vol 10 (11) ◽

pp. 996

Author(s):

Zhengxuan Liang ◽

Hongbo Chen ◽

Chenguang Wang ◽

Changquan Calvin Sun

Keyword(s):

Oxalic Acid ◽

Dissolution Rate ◽

Physical Stability ◽

Formulation Development ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

Conjugate Acid ◽

Enhanced Solubility ◽

Antihistamine Drug ◽

Low Solubility

Loratadine (Lor) is an antihistamine drug commonly used to relieve the symptoms of allergy. It has high permeability but low solubility under physiological conditions. To overcome the problem of low solubility, we synthesized and characterized two Loratadine multi-component crystalline phases with oxalic acid (Oxa), i.e., a 1:1 Lor-Oxa conjugate acid-base (CAB) cocrystal (Lor-Oxa CAB) and a 2:1 Lor-Oxa cocrystal monohydrate (Lor-Oxa hydrate). Both cocrystals exhibited an enhanced solubility and intrinsic dissolution rate (IDR) compared to Lor and adequate physical stability. The intrinsic dissolution rate of Lor-Oxa CAB is 95 times that of Lor, which makes it a promising candidate for tablet formulation development.

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An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2020.02.005 ◽

2020 ◽

Vol 150 ◽

pp. 24-32 ◽

Cited By ~ 3

Author(s):

Kelly Etherson ◽

Claire Dunn ◽

Wayne Matthews ◽

Henrik Pamelund ◽

Camille Barragat ◽

...

Keyword(s):

Dissolution Rate ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate

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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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A thermodynamic based approach on the investigation of a diflunisal pharmaceutical co-crystal with improved intrinsic dissolution rate

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2014.02.048 ◽

2014 ◽

Vol 466 (1-2) ◽

pp. 68-75 ◽

Cited By ~ 23

Author(s):

António O.L. Évora ◽

Ricardo A.E. Castro ◽

Teresa M.R. Maria ◽

M. Ramos Silva ◽

J.H. ter Horst ◽

...

Keyword(s):

Dissolution Rate ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate

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Variable-focus microscopy and UV surface dissolution imaging as complementary techniques in intrinsic dissolution rate determination

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2017.07.053 ◽

2017 ◽

Vol 530 (1-2) ◽

pp. 139-144 ◽

Cited By ~ 10

Author(s):

Adam Ward ◽

Karl Walton ◽

Karl Box ◽

Jesper Østergaard ◽

Lisa J. Gillie ◽

...

Keyword(s):

Dissolution Rate ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

Complementary Techniques ◽

Variable Focus

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The effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate of amlodipine besylate, using the rotating disk method

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502014000300009 ◽

2014 ◽

Vol 50 (3) ◽

pp. 513-520 ◽

Cited By ~ 2

Author(s):

Leandro Giorgetti ◽

Michele Georges Issa ◽

Humberto Gomes Ferraz

Keyword(s):

Dissolution Rate ◽

Rotation Speed ◽

Compaction Pressure ◽

Rotating Disk ◽

Fractional Factorial ◽

Amlodipine Besylate ◽

Dissolution Medium ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

Disk Method

The aim of this study was to evaluate the effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate (IDR) of the antihypertensive drug amlodipine besylate, using the rotating disk method. Accordingly, a fractional factorial design (33-1) was used, employing dissolution media (water, phosphate buffer pH 6.8 and HCl 0.1 M), rotation speed (50, 75 and 100 rpm), and compaction pressure (1000, 1500 and 2000 psi) as independent variables. The assays were randomized and statistically compared using the Statistica(r) 11 software program. Significance testing (ANOVA) indicated that the dissolution medium had a considerable impact on the IDR of amlodipine besylate. Analysis of the linear and quadratic components of the variables led to the proposition of a mathematical model that describes the IDR as a function of the parameters studied. Conversely, the levels of compaction pressure and rotation speed employed during experimental planning were less relevant, especially when the assay was conducted in the HCl 0.1 M medium.

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