Tannic acid as a co-former in co-amorphous systems: Enhancing their physical stability, solubility and dissolution behavior

This work assesses the stability and quality of Ciprofloxacin hydrochloride tablets after subjection to accelerated stability conditions of sunlight, temperature of 40±10C, 75% relative humidity, and UV light of 365 nm for 4 hours each day. This study was performed at time zero and at 4-day intervals for a period of 45 days (that is, days 0, 4, 8, 12…40, 44) according to the International Conference on Harmonization (ICH) accelerated aging conditions and the results obtained were subjected to statistical analysis. The results showed that with increasing time there was a gradual reduction in the dissolution rate with the tablets exposed to all four storage conditions failing the test on day 44 where they had less than 80 % release of the label claim. For content of Ciprofloxacin Hydrochloride, only those tablets exposed to UV light passed the test for all 44 days as they had a minimum of 96.83 % content on the 44th day. At day 0, all the tablets assayed passed this test, having a ciprofloxacin content of 99.43 %. For those tablets subjected to the other storage conditions including temperature of 40±10C, 75 % relative humidity and sunlight, they had ciprofloxacin content of 70.22 %, 71.50 %, and 78.36 % respectively. The results further, indicated that the storage conditions used in the study had a greater impact on the dissolution behavior and content of the Ciprofloxacin tablets than they did on the physical stability (hardness, uniformity of weight, disintegration).

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Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Pharmaceutics ◽

10.3390/pharmaceutics13101725 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1725

Author(s):

Jiawei Han ◽

Luyuan Li ◽

Meiling Su ◽

Weili Heng ◽

Yuanfeng Wei ◽

...

Keyword(s):

Physical Stability ◽

Drug Dissolution ◽

Amorphous Systems ◽

Polymer Addition ◽

Promising Strategy ◽

Crystallization Inhibition ◽

Water Wettability ◽

Long Time ◽

Enhanced Surface ◽

Pvp K30

Different from previously reported co-amorphous systems, a co-amorphous curcumin-magnolol (CUR-MAG CM) system, as compared with its crystalline counterparts, exhibited decreased dissolution due to its aggregation during dissolution. The main purpose of the present study is to deaggregate CUR-MAG CM to optimize drug dissolution and explore the deaggregation mechanism involved. Herein, a small amount of polymer (HPMC, HPC, and PVP K30) was co-formulated at 5% (w/w) with CUR-MAG CM as ternary co-amorphous systems. The polymer addition changed the surface properties of CUR-MAG CM including improved water wettability enhanced surface free energy, and hence exerted a deaggregating effect. As a result, the ternary co-amorphous systems showed faster and higher dissolution as compared with crystalline CUR/MAG and CUR-MAG CM. In addition, the nucleation and crystal growth of dissolved CUR and MAG molecules were significantly inhibited by the added polymer, maintaining a supersaturated concentration for a long time. Furthermore, polymer addition increased the Tg of CUR-MAG CM, potentially involving molecular interactions and inhibiting molecular mobility, resulting in enhanced physical stability under 25 °C/60% RH and 40 °C/75% RH conditions. Therefore, this study provides a promising strategy to optimize the dissolution and physical stability of co-amorphous systems by deaggregation and crystallization inhibition via adding small amounts of polymers.

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Physical Stability and Dissolution Behavior of Ketoconazole–Organic Acid Coamorphous Systems

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.8b00035 ◽

2018 ◽

Vol 15 (5) ◽

pp. 1862-1869 ◽

Cited By ~ 31

Author(s):

Michelle Fung ◽

Ka̅rlis Be̅rziņš ◽

Raj Suryanarayanan

Keyword(s):

Organic Acid ◽

Physical Stability ◽

Dissolution Behavior

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Transformations between Co-Amorphous and Co-Crystal Systems and Their Influence on the Formation and Physical Stability of Co-Amorphous Systems

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.8b01229 ◽

2019 ◽

Vol 16 (3) ◽

pp. 1294-1304 ◽

Cited By ~ 7

Author(s):

Wenqi Wu ◽

Yixuan Wang ◽

Korbinian Löbmann ◽

Holger Grohganz ◽

Thomas Rades

Keyword(s):

Physical Stability ◽

Amorphous Systems

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A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan

Molecules ◽

10.3390/molecules26040801 ◽

2021 ◽

Vol 26 (4) ◽

pp. 801

Author(s):

Rong Di ◽

Jingwen Liu ◽

Holger Grohganz ◽

Thomas Rades

Keyword(s):

Physical Stability ◽

Principal Component ◽

Water Soluble ◽

Mixing Ratio ◽

Scanning Calorimetry ◽

Amorphous Systems ◽

Amorphous System ◽

Novel Approach ◽

Water Soluble Drugs ◽

Optimal Mixing

Converting crystalline compounds into co-amorphous systems is an effective way to improve the solubility of poorly water-soluble drugs. It is, however, of critical importance for the physical stability of co-amorphous systems to find the optimal mixing ratio of the drug with the co-former. In this study, a novel approach for this challenge is presented, exemplified with the co-amorphous system carvedilol–tryptophan (CAR–TRP). Following X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) of the ball-milled samples to confirm their amorphous form, Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were applied to investigate intermolecular interactions. A clear deviation from a purely additive spectrum of CAR and TRP was visualized in the PCA score plot, with a maximum at around 30% drug (mol/mol). This deviation was attributed to hydrogen bonds of CAR with TRP ether groups. The sample containing 30% drug (mol/mol) was also the most stable sample during a stability test. Using the combination of FTIR with PCA is an effective approach to investigate the optimal mixing ratio of non-strong interacting co-amorphous systems.

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Characterization, Physical Stability, and Dissolution Behavior of Naringenin / Mannitol Solid Dispersions Prepared by Solvent Evaporation Method with Three Drying Methods

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.236-238.2264 ◽

2011 ◽

Vol 236-238 ◽

pp. 2264-2272

Author(s):

Guang Fa Wang ◽

Chun Lan Dai ◽

Zheng Gen Liao ◽

Guo Wei Zhao ◽

Xin Li Liang ◽

...

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Physical Stability ◽

Solvent Evaporation ◽

Vacuum Drying ◽

Dissolution Behavior ◽

Drying Methods ◽

Solvent Evaporation Method ◽

Evaporation Method ◽

Ft Ir

Solid dispersions (SD) were prepared with naringenin and mannitol by the solvent evaporation method with three drying methods (vacuum drying, VD; microwave-vacuum drying, MVD; and spray drying, SPD). The SD was characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (PXRD), Scanning Electronic Microscope (SEM), and Fourier Transform Infrared Spectroscopy (FT-IR).In vitrodissolution of naringenin and physical stability was investigated, and the energy consumption of different processing methods was measured. The results showed that the vitro dissolution rate and extent of naringenin was significantly improved by SD prepared with different drying methods compared to that of the pure drug and physical mixture (PM), and the dissolution rate of SD-SPD and SD-MVD was much higher than the SD-VD. The results of FT-IR showed that naringenin is possibly interacted with mannitol via intermolecular hydrogen bond; The PXRD showed that the crystallinity of the SD prepared with three drying methods was reduced sharply as compared with pure naringenin and PM. There results showed that the physical state of SD-MVD was more stable than SD-SPD and SD-VD that stored in the 40 °C/75% RH chamber in three month. Compared with other drying methods, the MVD method can save time and energy. These results suggest that MVD is feasible to replace the traditional time-consuming and low efficiency drying procedure for preparation of solid dispersions.

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