Solubility Advantage (and Disadvantage) of Pharmaceutical Amorphous Solid Dispersions

Huang, Siyuan; Chen, Mao; Williams, Robert O.; Yang, Chia-Yi

doi:10.1016/j.xphs.2016.08.017

Cited by 50 publications

(32 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, during dissolution, the situation becomes increasingly more complex. The simplest situation, where the drug is molecularly mixed with a poorly soluble polymer, has been recently modeled by Huang et al[30]. In their model, FH theory is used to describe the change in drug chemical potential upon mixing with the polymer, while the Gibbs-Duhem (GD) equation is employed to account for changes in drug chemical potential due to water absorption by the ASD.…”

Section: Discussionmentioning

confidence: 99%

“…This observation has considerable potential implications for amorphous drug delivery systems; if solubility suppression were to occur when a drug is mixed with a polymer, supersaturation will be impacted with consequences for crystallization kinetics as well as bioavailability. A recent thermodynamic analysis of drug-polymer blends provides support for the concept of reduced amorphous solubility in such systems[30].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tailoring supersaturation from amorphous solid dispersions

Taylor

2018

Journal of Controlled Release

101

View full text Add to dashboard Cite

The maximum achievable concentration of a drug in solution is dictated by the chemical potential of the solid form. Because an amorphous solid has a higher chemical potential than the corresponding crystal form, in the absence of phase transformations, a higher transient solubility is expected. However, the chemical potential of an amorphous drug can be reduced by mixing with another component. Therefore, upon mixing with a polymer to form an amorphous solid dispersion (ASD), the maximum solution concentration achieved can be potentially altered, in particular if the polymer is poorly soluble in the dissolution medium. Such changes in the chemical potential of the drug may be a critical factor in determining the maximum achievable solution concentration, and could alter the crystallization driving force of the drug. Therefore, the aim of this study was to gain insights into the impact of poorly soluble polymers on the "amorphous solubility" of drugs formulated as amorphous solid dispersions. Lopinavir was selected as a model drug with a low crystallization tendency, enabling determination of the amorphous solubility as a function of ASD composition. Model polymers included cellulose acetate (CA), CA phthalate (CAP), ethylcellulose (EC), Eudragit® RL PO (EUD), hydroxypropylmethylcellulose (HPMC), HPMC acetate succinate (HPMCAS), and HPMC phthalate (HPMCP). The "amorphous solubility" of the drug alone was determined and then the changes in maximum achievable concentration were measured as a function of drug loading. Drug-polymer interactions were characterized using infrared spectroscopy (IR), differential scanning calorimetry (DSC) and moisture sorption analysis. The results showed that the maximum achievable concentration ("amorphous solubility") of lopinavir varied with the extent of drug-polymer interactions, as well as the drug weight fraction in the ASD. This information is of great value when evaluating the maximum achievable concentration of amorphous systems formulated with pH responsive polymers, and should contribute to a broader understanding of drug phase behavior in the context of ASDs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tailoring supersaturation from amorphous solid dispersions

Taylor

2018

Journal of Controlled Release

101

View full text Add to dashboard Cite

show abstract

“…The in vivo pharmacokinetics (PK) studies suggested that the AUC 0–∞ and C max values of the solid dispersion were 13-fold and 7-fold larger than those obtained by the free drug, respectively; that is, the bioavailability of curcumin was significantly improved by such a solid dispersion form. This should be due to the fact that (i) crystalline curcumin was transferred into the amorphous form in the matrix, resulting in an apparent increase in its solubility [ 77 ]; and (ii) the application of lecithin improved the drug’s capability of permeating into the intestinal membrane and also enhanced its bioadhesion to the wall of the gastrointestinal tract [ 51 ]. At the same time, the amorphous solid dispersion of curcumin also improved the undesirable taste, smell, and color of the free drug.…”

Section: Physical Maskingmentioning

confidence: 99%

Developments in Taste-Masking Techniques for Traditional Chinese Medicines

Zheng

Yang

et al. 2018

Pharmaceutics

View full text Add to dashboard Cite

A variety of pharmacologically active substances, including chemotherapeutic drugs and the substances from traditional Chinese medicine (TCM), always exhibit potent bioactivities after oral administration. However, their unpleasant taste (such as bitterness) and/or odor always decrease patient compliance and thus compromise their curative efficacies in clinical application. Therefore, the developments of taste-masking techniques are of great significance in improving their organoleptic properties. However, though a variety of taste-masking techniques have been successfully used to mask the unpalatable taste of chemotherapeutic drugs, their suitability for TCM substances is relatively limited. This is mainly due to the fact that the bitter ingredients existing in multicomponent TCM systems (i.e., effective fractions, single Chinese herbs, and compound preparations) are always unclear, and thus, there is lack of tailor-made taste-masking techniques to be utilized to conceal their unpleasant taste. The relevant studies are also relatively limited. As a whole, three types of taste-masking techniques are generally applied to TCM, including (i) functional masking via sweeteners, bitter blockers, and taste modifiers; (ii) physical masking via polymer film-coating or lipid barrier systems; and (iii) biochemical masking via intermolecular interaction, β-cyclodextrin inclusion, or ion-exchange resins. This review fully summarizes the results reported in this field with the purpose of providing an informative reference for relevant readers.

show abstract

“…SDs have the advantages of reducing particle size, improved wettability, higher porosity degree, and amorphous structure for particles 24‐26 . The main demerit associated with this technique is its physical instability 27 …”

Section: Introductionmentioning

confidence: 99%

Solid dispersion systems engineered from hydroxypropyl‐β‐cyclodextrin and water‐soluble polymers for enhanced oral bioavailability of nimodipine

Boakye‐Yiadom

Kesse

Aquib

et al. 2020

Polymers for Advanced Techs

View full text Add to dashboard Cite

Nimodipine (NMD) is a calcium channel blocker that is used in the treatment of cerebrovascular disorders, such as stroke indicated for biological rhythm and neurological disorders. According to biopharmaceutical classification, NMD is categorized as a class ΙΙ drug, meaning it has a poor solubility profile. The objective of this experiment is to prepare multicomponent systems to enhance the solubility, dissolution, and bioavailability of NMD. Inclusion complex and solvent evaporation techniques have been exploited to overcome this challenge. in vitro dissolution studies and solubility, the profile was performed in three pH media (pH 7.5, 1.2, and 6.8). The drug release at (Q60min) for SD‐PVP3 was 33‐fold higher than pure NMD in double‐distilled water. The solubility of SD PVP3 was about 30 times higher than plain NMD in double‐distilled water. A pharmacokinetic study in rats indicated that the AUC0‐720 value of the inclusion complex (NMD‐KD) was 1.63‐fold higher than pure NMD. At the same time, the solid dispersion (NMD‐SD PVP3) was 3.94‐fold higher than that of plain NMD, indicating a significant increase in the bioavailability of NMD. The combination of the inclusion complex and solvent evaporation method led to the formation of new solid dispersions (SD PLX and SD PVP), which significantly increased the solubility, dissolution, and the oral bioavailability of NMD.

show abstract

Solubility Advantage (and Disadvantage) of Pharmaceutical Amorphous Solid Dispersions

Cited by 50 publications

References 36 publications

Tailoring supersaturation from amorphous solid dispersions

Tailoring supersaturation from amorphous solid dispersions

Developments in Taste-Masking Techniques for Traditional Chinese Medicines

Solid dispersion systems engineered from hydroxypropyl‐β‐cyclodextrin and water‐soluble polymers for enhanced oral bioavailability of nimodipine

Contact Info

Product

Resources

About