Impact of Hypromellose Acetate Succinate Grade on Drug Amorphous Solubility and In Vitro Membrane Transport

Ueda, Keisuke; Hate, Siddhi S.; Taylor, Lynne S.

doi:10.1016/j.xphs.2020.04.014

Cited by 31 publications

(28 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…8,62 Hence, varying the polymer type or polymer concentration can alter the nanodroplet properties and in turn, the dissolution rate or even the amorphous solubility of the nanodroplets. 63 Variability in the mass transport rate due to differences in the properties of additives was also recently reported for mass transport of fenofibrate nanocrystals across the mucin layer, wherein higher permeability was observed when HPMC with lower molecular weight was used as opposed to HPMC with higher molecular weight. 64 For ATZ, differences in the mass flow rate in solutions containing drug-rich nanodroplets have been reported for different grades of HPMCAS, 63 while a combination of HPMC and CTAB has been reported to reduce the amorphous solubility of ketoprofen.…”

Section: Contribution Of Drug-rich Nanodroplets To Membrane Mass Tran...mentioning

confidence: 68%

“…63 Variability in the mass transport rate due to differences in the properties of additives was also recently reported for mass transport of fenofibrate nanocrystals across the mucin layer, wherein higher permeability was observed when HPMC with lower molecular weight was used as opposed to HPMC with higher molecular weight. 64 For ATZ, differences in the mass flow rate in solutions containing drug-rich nanodroplets have been reported for different grades of HPMCAS, 63 while a combination of HPMC and CTAB has been reported to reduce the amorphous solubility of ketoprofen. 65 The impact of polymer or surfactant type on the properties of drug-rich nanodroplet is still an active area of research and certainly warrants careful consideration when evaluating mass transport of solutions containing drug-rich nanodroplets.…”

Section: Contribution Of Drug-rich Nanodroplets To Membrane Mass Tran...mentioning

confidence: 68%

See 1 more Smart Citation

A Mechanistic Study of Drug Mass Transport from Supersaturated Solutions Across PAMPA Membranes

Hate

Mosquera-Giraldo

Taylor

2022

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

Section: Contribution Of Drug-rich Nanodroplets To Membrane Mass Tran...mentioning

confidence: 68%

Section: Contribution Of Drug-rich Nanodroplets To Membrane Mass Tran...mentioning

confidence: 68%

A Mechanistic Study of Drug Mass Transport from Supersaturated Solutions Across PAMPA Membranes

Hate

Mosquera-Giraldo

Taylor

2022

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

“…Polymers or other components in solution can incorporate in the drug-rich phase thereby reducing the maximum achievable concentration. 15 , 23 , 24 The drug becomes diluted in the drug-rich phase, which determines the drug chemical potential. In fact, the co-existence of water, polymer, and drugs in the drug-rich phase forms a complex system that cannot be related to the solid-state mixture of amorphous multidrug formulation.…”

Section: Discussionmentioning

confidence: 99%

“… 22 The selection of the polymer is critical, as it may reduce the maximum achievable concentration of the drug if it partitions into the drug-rich phase. 23 , 24 Supersaturated formulations have a higher membrane transport than the crystalline-based ones because the supersaturated state has a higher thermodynamic activity than the saturated state. 16 , 25 , 26 Indeed, the increased amount of the dissolved drug due to the solubilization by biological fluid components or solubilizing agents does not increase the membrane transport rate of the drug.…”

Section: Introductionmentioning

confidence: 99%

Impact of Simulated Intestinal Fluids on Dissolution, Solution Chemistry, and Membrane Transport of Amorphous Multidrug Formulations

2021

View full text Add to dashboard Cite

The solution behavior and membrane transport of multidrug formulations were herein investigated in a biorelevant medium simulating fasted conditions. Amorphous multidrug formulations were prepared by the solvent evaporation method. Combinations of atazanavir (ATV) and ritonavir (RTV) and felodipine (FDN) and indapamide (IPM) were prepared and stabilized by a polymer for studying their dissolution (under non-sink conditions) and membrane transport in fasted state simulated intestinal fluid (FaSSIF). The micellar solubilization by FaSSIF enhanced the amorphous solubility of the drugs to different extents. Similar to buffer, the maximum achievable concentration of drugs in combination was reduced in FaSSIF, but the extent of reduction was affected by the degree of FaSSIF solubilization. Dissolution studies of ATV and IPM revealed that the amorphous solubility of these two drugs was not affected by FaSSIF solubilization. In contrast, RTV was significantly affected by FaSSIF solubilization with a 30% reduction in the maximum achievable concentration upon combination to ATV, compared to 50% reduction in buffer. This positive deviation by FaSSIF solubilization was not reflected in the mass transport–time profiles. Interestingly, FDN concentrations remain constant until the amount of IPM added was over 1000 μg/mL. No decrease in the membrane transport of FDN was observed for a 1:1 M ratio of FDN-IPM combination. This study demonstrates the importance of studying amorphous multidrug formulations under physiologically relevant conditions to obtain insights into the performance of these formulations after oral administration.

show abstract

“…An improved version of the WATERGATE method was used to suppress the signal from the water. 16,17 The method was directly adopted from Ueda et al 18 HPMCAS and Eudragit solutions were prepared by adding 10, 25, 50, 100, and 200 μg/mL of the respective polymer to the aqueous phase. These solutions were used to construct a linear standard curve for each polymer.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Interaction of Polymers with Enzalutamide Nanodroplets—Impact on Droplet Properties and Induction Times

et al. 2021

Self Cite

View full text Add to dashboard Cite

Amorphous solid dispersions (ASDs), which consist of a drug dispersed in a polymeric matrix, are increasingly being applied to improve the in vivo performance of poorly water-soluble drugs delivered orally. The polymer is a critical component, playing several roles including facilitating drug release from the ASD, as well as delaying crystallization from the supersaturated solution generated upon dissolution. Certain ASD formulations dissolve to produce amorphous drug-rich nanodroplets. The interaction of the polymer with these nanodroplets is poorly understood but is thought to be important for inhibiting crystallization in these systems. In this study, the impact of ionic polymers on the crystallization kinetics of enzalutamide from supersaturated solutions containing different amounts of amorphous nanodroplets was evaluated by determination of nucleation induction times. The amount of the polymer associated with the drug nanodroplets was also determined. When comparing two polymers, hydroxypropylmethyl cellulose acetate succinate (HPMCAS) and Eudragit E PO, it was found that the crystallization tendency and physical properties of the drug nanodroplets varied in the presence of these two polymers. Both polymers distributed between the aqueous phase and the drug-rich nanodroplets. A greater amount of Eudragit E PO was associated with the drug-rich nanodroplets. Despite this, Eudragit E PO was a less-effective crystallization inhibitor than HPMCAS in systems containing nanodroplets. In conclusion, in supersaturated solutions containing amorphous nanodroplets, the extent of association of a polymer with the drug nanodroplet does not solely predict crystallization inhibition.

show abstract

Impact of Hypromellose Acetate Succinate Grade on Drug Amorphous Solubility and In Vitro Membrane Transport

Cited by 31 publications

References 58 publications

A Mechanistic Study of Drug Mass Transport from Supersaturated Solutions Across PAMPA Membranes

A Mechanistic Study of Drug Mass Transport from Supersaturated Solutions Across PAMPA Membranes

Impact of Simulated Intestinal Fluids on Dissolution, Solution Chemistry, and Membrane Transport of Amorphous Multidrug Formulations

Interaction of Polymers with Enzalutamide Nanodroplets—Impact on Droplet Properties and Induction Times

Contact Info

Product

Resources

About