scholarly journals Amorphization of Thiamine Mononitrate: A Study of Crystallization Inhibition and Chemical Stability of Thiamine in Thiamine Mononitrate Amorphous Solid Dispersions

2020 ◽  
Vol 21 (24) ◽  
pp. 9370
Author(s):  
Seda Arioglu-Tuncil ◽  
Adrienne L. Voelker ◽  
Lynne S. Taylor ◽  
Lisa J. Mauer
Keyword(s):  
Chemical Stability ◽  
High Performance ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Moisture Sorption ◽  
Amorphous Solid ◽  
Storage Conditions ◽  
X Ray Diffraction ◽  
Salt Form ◽  
Crystallization Inhibition

This study investigated thiamine degradation in thiamine mononitrate (TMN):polymer solid dispersions, accounting for the physical state of the vitamin and the recrystallization tendency of TMN in these dispersions. Results were compared with those from solid dispersions containing a different salt form of thiamine (thiamine chloride hydrochloride (TClHCl)). TMN:polymer dispersions were prepared by lyophilizing solutions containing TMN and amorphous polymers (pectin and PVP (polyvinylpyrrolidone)). Samples were stored in controlled temperature and relative humidity (RH) environments for eight weeks and monitored periodically by X-ray diffraction and high performance liquid chromatography (HPLC). Moisture sorption, glass transition temperature (Tg), intermolecular interactions, and pH were also determined. Similar to the TClHCl:polymer dispersions, thiamine was more chemically labile in the amorphous state than the crystalline state, when present in lower proportions in amorphous TMN:polymer dispersions despite increasing Tg values, when environmental storage conditions exceeded the Tg of the dispersion, and when co-formulated with PVP compared to pectin. When thiamine remained as an amorphous solid, chemical stability of thiamine did not differ as a function of counterion present (TMN vs. TClHCl). However, storage at 75% RH led to hydration of thiamine:PVP dispersions, and the resulting pH of the solutions as a function of thiamine salt form led to a higher chemical stability in the acidic TClHCl samples than in the neutral TMN samples.

scholarly journals Amorphization of Thiamine Chloride Hydrochloride: Effects of Physical State and Polymer Type on the Chemical Stability of Thiamine in Solid Dispersions

2020 ◽  
Vol 21 (16) ◽  
pp. 5935 ◽  
Author(s):  
Seda Arioglu-Tuncil ◽  
Adrienne L. Voelker ◽  
Lynne S. Taylor ◽  
Lisa J. Mauer
Keyword(s):  
Intermolecular Interactions ◽  
Physical State ◽  
Amorphous Polymer ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Moisture Sorption ◽  
Storage Conditions ◽  
X Ray Diffraction ◽  
Unexplored Area ◽  
Polymer Dispersions

Thiamine is an essential micronutrient, but delivery of the vitamin in supplements or foods is challenging because it is unstable under heat, alkaline pH, and processing/storage conditions. Although distributed as a crystalline ingredient, thiamine chloride hydrochloride (TClHCl) likely exists in the amorphous state, specifically in supplements. Amorphous solids are generally less chemically stable than their crystalline counterparts, which is an unexplored area related to thiamine delivery. The objective of this study was to document thiamine degradation in the amorphous state. TClHCl:polymer dispersions were prepared by lyophilizing solutions containing TClHCl and amorphous polymers (pectin and PVP (poly[vinylpyrrolidone])). Samples were stored in controlled temperature (30–60 °C) and relative humidity (11%) environments for 8 weeks and monitored periodically by X-ray diffraction (to document physical state) and HPLC (to quantify degradation). Moisture sorption, glass transition temperature (Tg), intermolecular interactions, and pH were also determined. Thiamine was more labile in the amorphous state than the crystalline state and when present in lower proportions in amorphous polymer dispersions, despite increasing Tg values. Thiamine was more stable in pectin dispersions than PVP dispersions, attributed to differences in presence and extent of intermolecular interactions between TClHCl and pectin. The results of this study can be used to control thiamine degradation in food products and supplements to improve thiamine delivery and decrease rate of deficiency.

scholarly journals Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 438 ◽  
Author(s):  
Joanna Szafraniec-Szczęsny ◽  
Agata Antosik-Rogóż ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
Ewa Szefer ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Active Pharmaceutical Ingredient ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
High Propensity ◽  
Poorly Soluble ◽  
Amorphous Drug

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

scholarly journals Bioavailability Improvement of Carbamazepine via Oral Administration of Modified-Release Amorphous Solid Dispersions in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1023
Author(s):  
Houli Li ◽  
Meimei Zhang ◽  
Lilong Xiong ◽  
Weiyi Feng ◽  
Robert O. Williams
Keyword(s):  
Controlled Release ◽  
Oral Absorption ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Pharmacokinetic Studies ◽  
Modified Release ◽  
Capsule Formulation ◽  
Amorphous Solid Dispersions

The purpose of this study was to improve the bioavailability of carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, via modified-release amorphous solid dispersions (mr-ASD) by a thin film freezing (TFF) process. Three types of CBZ-mr-ASD with immediate-, delayed-, and controlled-release properties were successfully prepared with HPMC E3 (hydrophilic), L100-55 (enteric), and cellulose acetate (CA, lipophilic), defined as CBZ-ir-ASD, CBZ-dr-ASD, and CBZ-cr-ASD, respectively. A dry granulation method was used to prepare CBZ-mr-ASD capsule formulations. Various characterization techniques were applied to evaluate the physicochemical properties of CBZ-mr-ASD and the related capsules. The drug remained in an amorphous state when encapsulated within CBZ-mr-ASD, and the capsule formulation progress did not affect the performance of the dispersions. In dissolution tests, the preparations and the corresponding dosage forms similarly showed typical immediate-, delayed-, and controlled-release properties depending on the solubility of the polymers. Moreover, single-dose 24 h pharmacokinetic studies in rats indicated that CBZ-mr-ASD significantly enhanced the oral absorption of CBZ compared to that of crude CBZ. Increased oral absorption of CBZ was observed, especially in the CBZ-dr-ASD formulation, which showed a better pharmacokinetic profile than that of crude CBZ with 2.63- and 3.17-fold improved bioavailability of the drug and its main active metabolite carbamazepine 10,11-epoxide (CBZ-E).

scholarly journals Enhanced Dissolution Efficiency of Tamoxifen Combined with Methacrylate Copolymers in Amorphous Solid Dispersions

Crystals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1046
Author(s):  
Dayanne T. C. da Silva ◽  
Daniela Nadvorny ◽  
Lucas J. de A. Danda ◽  
Amanda C. Q. de M. Vieira ◽  
Patricia Severino ◽  
...  
Keyword(s):  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Physical Mixture ◽  
Polymer Mixture ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Acrylate Copolymer ◽  
Poorly Soluble

Amorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen–polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit® L 100 and Eudragit® RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems.

scholarly journals Physical Compatibility and Chemical Stability of Injectable and Oral Ranitidine Solutions

2018 ◽  
Vol 54 (1) ◽  
pp. 32-36
Author(s):  
Kelly Fleming ◽  
Ronald F. Donnelly
Keyword(s):  
High Performance Liquid Chromatography ◽  
Chemical Stability ◽  
High Performance ◽  
Storage Conditions ◽  
Hplc Method ◽  
Physical Parameters ◽  
Ranitidine Hydrochloride ◽  
Unit Dose ◽  
Stability Results ◽  
Collection Time

Objectives: The physical compatibility and chemical stability of ranitidine hydrochloride injectable solutions and oral syrup were studied to define beyond-use dates (BUDs). Methods: Ranitidine hydrochloride injectable solutions of 25 mg/mL packaged in glass vials and 5 mg/mL in polypropylene (PP) syringes were prepared in triplicate. Samples were refrigerated and protected from light (PFL) or stored at 25°C and either exposed to light (ETL) or PFL. Ranitidine hydrochloride oral syrup 15 mg/mL in unit-dose amber PP syringes were prepared in triplicate and then kept at 25°C. Samples were collected at days 0, 7, 14, 28, 56, and 91. Additional samples were collected at 6 months and at 6, 9, and 12 months for the 25 mg/mL solution and oral syrup, respectively. Physical parameters of pH, clarity, and color were obtained at each collection time. A validated stability-indicating high-performance liquid chromatography (HPLC) method was used to determine the chemical stability. Results: Formulations had no significant change in pH or clarity. Although some samples yellowed, this was not associated with a decrease in concentration. The 25 mg/mL solution remained above 98.6% for 6 months, whereas the 5 mg/mL solution remained above 93.5% for 91 days under all storage conditions. At 25°C, the oral syrup retained greater than 98.8% for 12 months. Conclusions: The ranitidine hydrochloride injectable solutions were stable for 6 months and 91 days under the 3 storage conditions, respectively, for the 25 mg/mL solution in glass vials and 5 mg/mL solution in PP syringes. The 15 mg/mL oral syrup in unit-dose amber PP syringes was stable for 12 months at 25°C and PFL.

scholarly journals A Novel Protocol Using Small-Scale Spray-Drying for the Efficient Screening of Solid Dispersions in Early Drug Development and Formulation, as a Straight Pathway from Screening to Manufacturing Stages

2018 ◽  
Vol 11 (3) ◽  
pp. 81
Author(s):  
Aymeric Ousset ◽  
Rosanna Chirico ◽  
Florent Robin ◽  
Martin Schubert ◽  
Pascal Somville ◽  
...  
Keyword(s):  
Spray Drying ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Screening Strategy ◽  
Water Soluble ◽  
Small Scale ◽  
Absorption Window

This work describes a novel screening strategy that implements small-scale spray-drying in early development of binary amorphous solid dispersions (ASDs). The proposed methodology consists of a three-stage decision protocol in which small batches (20–100 mg) of spray-dried solid dispersions (SDSDs) are evaluated in terms of drug–polymer miscibility, physical stability and dissolution performance in bio-predictive conditions. The objectives are to select the adequate carrier and drug-loading (DL) for the manufacturing of robust SDSD; and the appropriate stabilizer dissolved in the liquid vehicle of SDSD suspensions, which constitutes the common dosage form used during non-clinical studies. This methodology was verified with CDP146, a poorly water soluble (<2 µg/mL) API combined with four enteric polymers and four stabilizers. CDP146/HPMCAS-LF 40:60 (w/w) and 10% (w/v) PVPVA were identified as the lead SDSD and the best performing stabilizer, respectively. Lead SDSD suspensions (1–50 mg/mL) were found to preserve complete amorphous state during 8 h and maintain supersaturation in simulated rat intestinal fluids during the absorption window. Therefore, the implementation of spray-drying as a small-scale screening approach allowed maximizing screening effectiveness with respect to very limited API amounts (735 mg) and time resources (9 days), while removing transfer steps between screening and manufacturing phases.

Physical and chemical stability of cytarabine in polypropylene syringes

2020 ◽  
pp. 107815522093740
Author(s):  
Wiem Ben Ayed ◽  
Chema Drira ◽  
Mohamed Ali Soussi ◽  
Hanen Ouesleti ◽  
Besma Hamdene ◽  
...  
Keyword(s):  
Chemical Stability ◽  
High Performance ◽  
Limit Of Detection ◽  
Physical Stability ◽  
Storage Conditions ◽  
Forced Degradation ◽  
Chromatography Method ◽  
Stability Indicating ◽  
Glass Containers ◽  
Physical And Chemical

Background Cytarabine is widely used to treat leukemia and lymphoma. Currently, Cyrabol®, powder for injection, is one of the specialties marketed in Tunisia. However, no stability data when diluted with 0.9% NaCl are available. The aim of this study is to evaluate the physical and chemical stability of cytarabine (Cyrabol®) solution after dilution in 0.9% NaCl (1 mg/mL, 5 mg/mL and 10 mg/mL) in polypropylene syringes under different storage conditions. Methods Cytarabine solutions (1 mg/mL, 5 mg/mL and 10 mg/mL) in 0.9% NaCl were prepared in polypropylene syringes and stored for 28 days under different conditions. Cytarabine preparations in glass containers were prepared as a control to detect any adsorption. Chemical stability was assessed by a stability-indicating high-performance liquid chromatography method. The stability-indicating capacity of the method was proved by forced degradation tests. Linearity, precision and limit of detection and quantification were performed according to the International Conference on Harmonisation recommendations. Physical stability was checked by visual inspection. Results The method was proven to be a validated stability-indicating assay. At 2–8°C, all tested solutions were chemically stable for 28 days. However, at 25°C, the main degradation product gradually increased during the study and the chemical stability of 1 mg/mL, 5 mg/mL and 10 mg/mL solutions was 14 days, 8 days and 5 days, respectively. Similar results were observed in the glass containers. Conclusion The highest physical and chemical stability of cytarabine diluted in 0.9% NaCl in polypropylene syringes was observed at 2–8°C. At 25°C, better stability was found in the 1 mg/mL solution compared with those at higher concentrations (5 mg/mL and 10 mg/mL).

AMORPHOUS SOLID DISPERSIONS OF PIOGLITAZONE HYDROCHLORIDE USING CREMOPHOR RH 40 AND POLOXAMER 188: IN VITRO AND IN VIVO EVALUATION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (01) ◽  
pp. 45-55
Author(s):  
R. P Swain ◽  
B. B Subudhi ◽  
Keyword(s):  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
In Vivo Evaluation ◽  
In Vivo Test ◽  
Water Soluble Drug

The study was aimed to improve dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water soluble drug. TGA showed compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns and SEM indicated change from crystalline to amorphous state. Prevention of recrystallization during storage suggested stability of formulation. Cremophor RH 40 based SD (solvent method) remarkably increased the dissolution within 15 min and was supported by dissolution parameters (Q15, IDR, RDR, % DE, f1, f2). In vivo test showed significantly (p < 0.05) higher AUC0-t and Cmax, which were about 4.46 and 4.84 times that of pure drug, respectively. Cremophor RH 40 was found to be a suitable carrier for SM for preparation of SDs of PH as evident from increased dissolution and bioavailability.

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