Hygroscopicity and Moisture Adsorption Kinetics of Pharmaceutical Solids: A Review

Umprayn, Kaisri; Mendes, Robert W.

doi:10.3109/03639048709105213

Cited by 51 publications

(14 citation statements)

References 58 publications

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“…The fact that an IPA content of 2.5% to 3.0% was retained in the system during storage at 68% RH may indicate that the clathrate warfarin sodium was converted partially to the amorphous form. This may be similar to the situation found with proteins, where the plasticizing effect may stop when the hydrogen bonding capacity of the solid is exceeded (8,9,11,12). At 75% RH or above, the clathrate deliquesced within 72 hours.…”

Section: Effect Of Water On Physical Stabilitysupporting

confidence: 48%

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Physical chemical stability of warfarin sodium

Gao

Maurin

2001

AAPS PharmSci

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Crystalline warfarin sodium is an isopropanol clathrate containing 8.3% isopropyl alcohol (IPA) and 0.57% water upon receipt. The hygroscopicity and impact of moisture on IPA status as well as on the stability of the clathrate was studied at different relative humidities. The IPA loss and water uptake were simultaneous but they did not exchange at 1:1 molar ratio. At 58% relative humidity (RH) or below, the exchange process was insignificant. At 68% RH or above, the clathrate tended to lose IPA while absorbing water and reverting to the amorphous state. The rate of IPA loss and moisture uptake was a function of RH. The thermal stability of the crystalline warfarin sodium was also examined. Physical change occurred after isothermal storage for 24 hours at 80oC and 11 hours at 120oC. The rate of IPA loss was temperature dependent.

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Section: Effect Of Water On Physical Stabilitysupporting

confidence: 48%

“…This may be because of the lack of the periodic structure in the system; thus, it provides more opportunity to accommodate water (8). According to Franks (9) and Hancock, et al (12), the process may also be considered as a plasticizing effect where water is a plasticizer.…”

Section: Effect Of Water On Physical Stabilitymentioning

confidence: 99%

Physical chemical stability of warfarin sodium

Gao

Maurin

2001

AAPS PharmSci

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“…5, experimentally measured moisture sorption isotherms for Sample A and Sample B showed a typical isotherm of type II, commonly reported for water insoluble hydrophilic polymers. 17) It is suspected that hydroxyl groups in the FK888 solid may have a similar role to that of water insoluble hydrophilic polymers. In addition, it appeared that the moisture sorption-desorption isotherms of Sample A and Sample B exhibited a hysteresis, showing that the amounts of water associated with the samples are greater for the desorption isotherm than for the adsorption isotherm at the given relative humidity.…”

Section: Resultsmentioning

confidence: 99%

Effect of Structural Relaxation on the Physical and Aerosol Properties of Amorphous Form of FK888 (NK1 Antagonist)

Tanaka

Kitamura

Kitagawa

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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The use of amorphous form of drug substances to improve solubility, accelerate dissolution, and promote therapeutic activity has been very important for the development for water insoluble solids as pharmaceutical dosage forms. 1)However, not only chemical degradation 2) but also physical change such as crystallization 3,4) and aggregation 5,6) of amorphous solids even below their glass transition temperature (Tg) were reported, and these instabilities of most amorphous solids preclude their more widespread use in pharmaceutical dosage forms. Such advantages and disadvantages are offered due to excess properties of amorphous systems in terms of enthalpy and free energy. These high energy systems are unstable and tend to spontaneously revert back to the thermodynamically stable state. Thus, amorphous solids may crystallize, or even if crystallization does not occur on pharmaceutical shelf life, amorphous solids will 'relax' toward the equilibrium supercooled liquid state as shown in Fig. 1. As a glass moves towards the equilibrium state, energy decreases, free volume decreases, and structural order increases, i.e., configurational entropy decreases. Thus, this process is called structural relaxation. As the intact amorphous state indicated in Fig. 1 is of higher enthalpy than the equilibrium state, heat is given off during the relaxation process, and this process is known as enthalpy relaxation. This process has strong temperature dependence, and the relaxation rate is maximal close to the Tg while negligible relaxation occurs at temperatures far below it. This means that relaxation of the amorphous materials would occur during pharmaceutical unit operations involving thermal or mechanical stresses. For glassy polymers, time dependent changes in physical and mechanical properties are often attributed to relaxation.7) This includes increase in density, yield stress, and modulus and decrease in creep and stress relaxation rate.8) Aging procedure is also known to increase the brittleness and lower the impact strength of glasses. 9)Thus, there is a large possibility that aging should affect the physical properties of amorphous solids, and those studies in pharmaceutical systems have focused on the measurement of relaxation times in relation to the stability prediction based on their molecular mobility. 10,11) Despite that amorphous drug substances can take various enthalpy states, there are few studies 12) to investigate its effect on their properties. FK888 (NK1 antagonist) is a candidate drug for migraine, and is developed as dry powder inhalers (DPIs) to avoid the first-pass effect and minimize unwanted side effects. The solid state of FK888 drug substance is adopted to be amorphous considering its low solubility in aqueous solution, and it is confirmed that the amorphous state is obtained constantly in industrial scale size. In the dosage form of DPIs, because the respirable fraction of the emitted dose is largely dependent on the geometric size of bulk drug particles, not * To whom correspondence should be addre...

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“…84 Para confirmação da formação de um cocristal e diferenciação em relação a outros cristais multicomponentes, diversas técnicas de caracterização no estado sólido podem ser empregadas, como difração de raios X (DRX), 85,86 análise térmica (Calorimetria Exploratória Diferencial -DSC e Termogravimetria -TGA), 1,86,87 microscopia, 88,89 espectroscopia vibracional (Raman e Infravermelho), 86,90 espectroscopia do estado sólido (Ressonância magnética nuclear do estado sólido -RMNss) 86,91-93 e análise de sorção de umidade. [94][95][96][97] …”

Section: Estratégias De Formação De Cocristaisunclassified

Cocristais: uma estratégia promissora na área farmacêutica

et al. 2016

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COCRYSTALS: A PROMISING STRATEGY IN PHARMACEUTICAL SCIENCES. Pharmaceutical cocrystals have emerged as a useful strategy to improve the aqueous solubility of poorly water soluble drugs by aiming to enhance their oral absorption and bioavailability. Aqueous cocrystal solubility can be orders of magnitude higher than that of the constituent drug and this solubility advantage can be fine-tuned based on environmental conditions such as pH and the presence of drug solubilizing agents. This review presents a brief overview of pharmaceutical cocrystals regarding cocrystal design, obtainment methods, with particular focus on cocrystal solubility, and the solubility modulation by solution phase chemistry.Keywords: cocrystals; drug; solubility; transition point; thermodynamic stability. INTRODUÇÃOO setor de fármaco-medicamentos representa uma área estratégica sob o ponto de vista tecnológico/produtivo nacional. Vários são os desafios da produção de medicamentos competitivos e de qualidade no Brasil, como a oferta de insumos, a pesquisa de novas moléculas ativas e a sua inserção no mercado. Neste sentido, a utilização de inovações incrementais surge como alternativa à problemática do setor, destacando-se a manipulação da forma cristalina dos fármacos, síntese de polimorfos, sais, complexos e, mais recentemente, os cocristais. 1 Cocristais são materiais cristalinos homogêneos, compostos por dois ou mais compostos em proporção estequiométrica definida e que são sólidos em condições ambientes (25 ºC/1 atm). 2,3 Ao longo das últimas décadas, os cocristais têm recebido atenção significativa por parte da indústria farmacêutica, e diversos cocristais farmacêuticos têm sido relatados. Cocristais farmacêuticos, por sua vez, são compostos por um ingrediente farmacêutico ativo (IFA) e uma molécula não tóxica ou outro IFA, chamado de coformador. Ligações de hidrogênio entre as moléculas neutras do fármaco e do coformador orientam a formação do cocristal. 2,4 A síntese de cocristais tem sido uma estratégia cada vez mais utilizada para melhorar a solubilidade, a taxa de dissolução in vitro, e consequentemente, a biodisponibilidade de fármacos pouco solúveis, sem a necessidade de mudar a estrutura molecular e/ou a interação farmacológica. [5][6][7] No entanto, a avaliação da solubilidade e estabilidade dos cocristais em solução ainda não está consolidada. Um levantamento realizado no período de 1999 a 2015 (Figura 1) revelou um crescente número de publicações envolvendo a síntese e a caracterização dos cocristais, mas um reduzido número de publicações envolvendo outros aspectos essenciais no desenvolvimento de formulações contendo cocristais, como estudos de solubilidade, química em solução, estabilidade e a influência de excipientes.Considerando que a baixa solubilidade aquosa é um dos principais problemas associados às entidades químicas farmacêuticas, os

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Hygroscopicity and Moisture Adsorption Kinetics of Pharmaceutical Solids: A Review

Cited by 51 publications

References 58 publications

Physical chemical stability of warfarin sodium

Physical chemical stability of warfarin sodium

Effect of Structural Relaxation on the Physical and Aerosol Properties of Amorphous Form of FK888 (NK1 Antagonist)

Cocristais: uma estratégia promissora na área farmacêutica

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