Correlation between drug dissolution and resistance to water-induced phase separation in solid dispersion formulations revealed by solid-state NMR spectroscopy

Okada, Hitomi; Ueda, Keisuke; Yasuda, Yuki; Higashi, Kenjirou; Inoue, Motoki; Ito, Masataka; Noguchi, Shuji; Kawakami, Kenji; Moribe, Kunikazu

doi:10.1016/j.ijpharm.2020.119086

Cited by 18 publications

(18 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the role of high energy amorphous form stabilized within the HPMC matrix in generating the supersaturated solutions cannot be overemphasized. Okada et al, (2020) observed that upon dissolution of Nifedipine/HPMC solid dispersion, the Nifedipine undergoes phase separation and dissolves independent of HPMC from amorphous Nifedipine rich phase (133). Furthermore, the unique property of glassy HPMC to swell in contact with water is exploited to extend the release of certain APIs through solid dispersion technology.…”

Section: Hydroxy Propyl Methyl Cellulose (Hpmc)mentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

View full text Add to dashboard Cite

Solid dispersion is the preferred technology to prepare efficacious forms of BCS class-II/IV APIs. To prepare solid dispersions, there exist a wide variety of polymeric carriers with interesting physicochemical and thermochemical characteristics available at the disposal of a formulation scientist. Since the advent of the solid dispersion technology in the early 1960s, there have been more than 5000 scientific papers published in the subject area. This review discusses the polymeric carrier properties of most extensively used polymers PVP, Copovidone, PEG, HPMC, HPMCAS, and Soluplus® in the solid dispersion technology. The literature trends about preparation techniques, dissolution, and stability improvement are analyzed from the Scopus® database to enable a formulator to make an informed choice of polymeric carrier. The stability and extent of dissolution improvement are largely dependent upon the type of polymeric carrier employed to formulate solid dispersions. With the increasing acceptance of transfer dissolution setup in the research community, it is required to evaluate the crystallization/precipitation inhibition potential of polymers under dynamic pH shift conditions. Further, there is a need to develop a regulatory framework which provides definition and complete classification along with necessarily recommended studies to characterize and evaluate solid dispersions.

show abstract

Section: Hydroxy Propyl Methyl Cellulose (Hpmc)mentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The amorphous system is a promising formulation strategy for increasing the solubility of drugs. Amorphous drugs have disordered structures and a higher Gibbs free energy than their crystalline counterparts [5]. Therefore, forming a supersaturated solution in the amorphous drug after being dispersed in water improves oral bioavailability [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Amorphous drugs have disordered structures and a higher Gibbs free energy than their crystalline counterparts [5]. Therefore, forming a supersaturated solution in the amorphous drug after being dispersed in water improves oral bioavailability [5,6]. However, the amorphous drug formulation is thermodynamically unstable and easily recrystallized during storage or its aqueous dispersion, thereby negating the advantages of enhanced solubility [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

Budiman

Aulifa

2022

Pharmaceuticals

View full text Add to dashboard Cite

The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form. However, the drug within MPS has shown incomplete release, despite a supersaturated solution being generated. This indicates the determination of maximum drug loading in MPS below what is experimentally necessary to maximize the drug doses in the system. Therefore, this study aimed to characterize the drugs with good glass former loaded-mesoporous silica, determine the maximum drug loading, and compare its theoretical value relevance to monolayer covering the mesoporous (MCM) surface, as well as pore-filling capacity (PFC). Solvent evaporation and melt methods were used to load each drug into MPS. In addition, the glass transition of ritonavir (RTV) and cyclosporine A (CYP), as well as the melting peak of indomethacin (IDM) and saccharin (SAC) in mesoporous silica, were not discovered in the modulated differential scanning calorimetry (MDSC) curve, demonstrating that each drug was successfully incorporated into the mesopores. The amorphization of RTV-loaded MPS (RTV/MPS), CYP-loaded MPS (CYP/MPS), and IDM-loaded MPS (IDM/MPS) were confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the MDSC curve. Additionally, the good glass formers, nanoconfinement effect of MPS and silica surface interaction contributed to the amorphization of RTV, CYP and IDM within MPS. Meanwhile, the crystallization of SAC was observed in SAC-loaded MPS (SAC/MPS) due to its weak silica surface interaction and high recrystallization tendency. The maximum loading amount of RTV/MPS was experimentally close to the theoretical amount of MCM, showing monomolecular adsorption of RTV on the silica surface. On the other hand, the maximum loading amount of CYP/MPS and IDM/MPS was experimentally lower than the theoretical amount of MCM due to the lack of surface interaction. However, neither CYP or IDM occupied the entire silica surface, even though some drugs were adsorbed on the MPS surface. Moreover, the maximum loading amount of SAC/MPS was experimentally close to the theoretical amount of PFC, suggesting the multilayers of SAC within the MPS. Therefore, this study demonstrates that the characterization of drugs within MPS, such as molecular size and interaction of drug-silica surface, affects the loading efficiency of drugs within MPS that influence its relevance with the theoretical value of drugs.

show abstract

“…Forster et al have reported the composition dependent presence of single or multiple T g values in the system of lacidipine and indomethacin with PVP . Apart from the presence of multiple T g values, reports also state the presence of a single T g as a sign of the molecularly dispersed ASD. ,− This is one of the commonly used qualitative predictors of drug-polymer miscibility with more than 50 instances in the reviewed literature. In a most recent report, Blasi et al have reported the presence of multiple T g values for ASD with ketoprofen content more than 35% w/w in poly(D, L-lactide- co -glycolide) …”

Section: Methods For the Evaluation Of Drug-polymer Solubility And Mi...mentioning

confidence: 99%

Analytical and Computational Methods for the Determination of Drug-Polymer Solubility and Miscibility

et al. 2021

View full text Add to dashboard Cite

In the pharmaceutical industry, poorly water-soluble drugs require enabling technologies to increase apparent solubility in the biological environment. Amorphous solid dispersion (ASD) has emerged as an attractive strategy that has been used to market more than 20 oral pharmaceutical products. The amorphous form is inherently unstable and exhibits phase separation and crystallization during shelf life storage. Polymers stabilize the amorphous drug by antiplasticization, reducing molecular mobility, reducing chemical potential of drug, and increasing glass transition temperature in ASD. Here, drug-polymer miscibility is an important contributor to the physical stability of ASDs. The current Review discusses the basics of drug-polymer interactions with the major focus on the methods for the evaluation of solubility and miscibility of the drug in the polymer. Methods for the evaluation of drug-polymer solubility and miscibility have been classified as thermal, spectroscopic, microscopic, solid–liquid equilibrium-based, rheological, and computational methods. Thermal methods have been commonly used to determine the solubility of the drug in the polymer, while other methods provide qualitative information about drug-polymer miscibility. Despite advancements, the majority of these methods are still inadequate to provide the value of drug-polymer miscibility at room temperature. There is still a need for methods that can accurately determine drug-polymer miscibility at pharmaceutically relevant temperatures.

show abstract

Correlation between drug dissolution and resistance to water-induced phase separation in solid dispersion formulations revealed by solid-state NMR spectroscopy

Cited by 18 publications

References 55 publications

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

Analytical and Computational Methods for the Determination of Drug-Polymer Solubility and Miscibility

Contact Info

Product

Resources

About