Utility of plasticised polymer in solid dispersions for solubility enhancement of thermosensitive and poorly soluble API

Kulthe, Viraj Vitthal; Chaudhari, Pravin D.; Chakraborty, Sayantani

doi:10.1016/j.jopr.2013.05.007

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…3) suggested residual crystallinity (18), and it was calculated to be 23.76 and 31.47%, respectively, by using equation 1 (Table II). On the other hand, occurrence of only one Tg at reduced onset temperature of about 218.7°C, and change in heat capacity suggested amorphous molecular dispersions of ACT within POL (18,19). This ratio also reported the least percent crystallinity of 13.95%, among the three ratios.…”

Section: Discussionmentioning

confidence: 81%

Effectiveness of Spray Congealing to Obtain Physically Stabilized Amorphous Dispersions of a Poorly Soluble Thermosensitive API

Kulthe

Chaudhari

2014

AAPS PharmSciTech

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Abstract. An amorphous phase produced by micronization up to the molecular or colloidal level of a poorly soluble drug having low lipophilicity can distinctly enhance its solubility characteristics. However, though dispersing the molten mass of a poorly water-soluble drug within polymeric matrix has been found to be most effective in formation of molecular dispersions, the drug molecules which melt at high temperature also accompanied by decomposition, such as acetazolamide, are difficult to formulate as molecular dispersions. Hence, a method is proposed to obtain molecular dispersions of acetazolamide with poloxamer-237 by spray congealing under optimal heat treatment. Uniform molecular and/or colloidal dispersions of the drug were achieved with instantaneous solvent evaporation by mixing a drug solution with molten mass of the plasticizer matrix. Immobilization of dispersed drug molecules was effected subsequently through rapid solidification by spray congealing. Initial characterization of 1:1, 1:1.5, and 1:2 ratios of solid dispersions and devitrification study of an optimized (1:2) ratio ensured efficacy of the proposed method in formation of physically stabilized amorphous systems without thermal degradation and hence resulted in more than ninefold rise in solubility and more than 90% dissolution within initial 10 min. With 1:2 ratio, molecular dispersions could be achieved by initial solvent evaporation stage, which when subjected to spray congealing produced physically stable amorphous systems, without signs of thermal degradation. This study also proposes an opportunity for selection of those polymers with which the drug is immiscible in their fluid state, yet obtaining molecular dispersions.

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Section: Discussionmentioning

confidence: 81%

Effectiveness of Spray Congealing to Obtain Physically Stabilized Amorphous Dispersions of a Poorly Soluble Thermosensitive API

Kulthe

Chaudhari

2014

AAPS PharmSciTech

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“…Cholestyramine was used as a complexing agent in the stoichiometric ratio of 1:1 (drug: resin). The saturation solubility studies showed an improvement in the solubility by ~ 3.25 fold following the amorphous conversion of the drug [ 114 ]. Panraksa et al .…”

Section: Drug-resin Complexes (Drc)mentioning

confidence: 99%

Drug complexes: Perspective from Academic Research and Pharmaceutical Market

et al. 2023

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Despite numerous research efforts, drug delivery through the oral route remains a major challenge to formulation scientists. The oral delivery of drugs poses a significant challenge because more than 40% of new chemical entities are practically insoluble in water. Low aqueous solubility is the main problem encountered during the formulation development of new actives and for generic development. A complexation approach has been widely investigated to address this issue, which subsequently improves the bioavailability of these drugs. This review discusses the various types of complexes such as metal complex (drug-metal ion), organic molecules (drug-caffeine or drug-hydrophilic polymer), inclusion complex (drug-cyclodextrin), and pharmacosomes (drug-phospholipids) that improves the aqueous solubility, dissolution, and permeability of the drug along with the numerous case studies reported in the literature. Besides improving solubility, drug-complexation provides versatile functions like improving stability, reducing the toxicity of drugs, increasing or decreasing the dissolution rate, and enhancing bioavailability and biodistribution. Apart, various methods to predict the stoichiometric ratio of reactants and the stability of the developed complex are discussed. Graphical Abstract

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“…The physicochemical properties of an API have a direct impact on its processing, delivery and therapeutic performance [10]. Currently, various formulation strategies have been utilized to improve the drug absorption and thus bioavailability, including milling [11]; self-emulsification [12]; solid dispersion [13]; hot melt extrusion [14]; inclusion complex [15]; nanoparticles [16]; liposomal formulations [17]; chemical modifications; and formation of other crystalline solids such as salts, hydrates and polymorphs; however, there are some limitations for each strategy. For example, salt is not practical for those very weakly ionized or nonionized compounds.…”

Section: Name Of T-apismentioning

confidence: 99%

Improving the Physicochemical and Biopharmaceutical Properties of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicine through Cocrystal Engineering

et al. 2021

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Active pharmaceutical ingredients (APIs) extracted and isolated from traditional Chinese medicines (TCMs) are of interest for drug development due to their wide range of biological activities. However, the overwhelming majority of APIs in TCMs (T-APIs), including flavonoids, terpenoids, alkaloids and phenolic acids, are limited by their poor physicochemical and biopharmaceutical properties, such as solubility, dissolution performance, stability and tabletability for drug development. Cocrystallization of these T-APIs with coformers offers unique advantages to modulate physicochemical properties of these drugs without compromising the therapeutic benefits by non-covalent interactions. This review provides a comprehensive overview of current challenges, applications, and future directions of T-API cocrystals, including cocrystal designs, preparation methods, modifications and corresponding mechanisms of physicochemical and biopharmaceutical properties. Moreover, a variety of studies are presented to elucidate the relationship between the crystal structures of cocrystals and their resulting properties, along with the underlying mechanism for such changes. It is believed that a comprehensive understanding of cocrystal engineering could contribute to the development of more bioactive natural compounds into new drugs.

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Utility of plasticised polymer in solid dispersions for solubility enhancement of thermosensitive and poorly soluble API

Cited by 4 publications

References 10 publications

Effectiveness of Spray Congealing to Obtain Physically Stabilized Amorphous Dispersions of a Poorly Soluble Thermosensitive API

Effectiveness of Spray Congealing to Obtain Physically Stabilized Amorphous Dispersions of a Poorly Soluble Thermosensitive API

Drug complexes: Perspective from Academic Research and Pharmaceutical Market

Improving the Physicochemical and Biopharmaceutical Properties of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicine through Cocrystal Engineering

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