Mechanism of Enhanced Nifedipine Dissolution by Polymer-Blended Solid Dispersion through Molecular-Level Characterization

Ueda, Keisuke; Yamazoe, Chisato; Yasuda, Yuki; Higashi, Kenjirou; Kawakami, Kenji; Moribe, Kunikazu

doi:10.1021/acs.molpharmaceut.8b00523

Cited by 29 publications

(27 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nifedipine (NDP) is a typical poorly water-soluble drug that is pharmaceutically used as a calcium channel blocker for the treatment of cardiovascular diseases [ 1 ]. Because of its poor water solubility (<5 μg/mL) [ 2 ], its dissolution and subsequent oral absorption are limited [ 3 , 4 ]. Therefore, its solubility must be enhanced via various formulations [ 2 , 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Because of its poor water solubility (<5 μg/mL) [ 2 ], its dissolution and subsequent oral absorption are limited [ 3 , 4 ]. Therefore, its solubility must be enhanced via various formulations [ 2 , 3 , 4 , 5 ]. The term “dispersion” refers to a drug in a polymer matrix or inert carrier [ 6 ] as a solid dispersion caused by the use of a meltable compound followed by solvent evaporation or melting solvent methods.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Improvement in Solubility and Absorption of Nifedipine Using Solid Solution: Correlations between Surface Free Energy and Drug Dissolution

Tubtimsri

Weerapol

2021

Polymers

View full text Add to dashboard Cite

Ternary solid solutions composed of nifedipine (NDP), amino methacrylate copolymer (AMCP), and polysorbate (PS) 20, 60, or 65 were prepared using a solvent evaporation method. The dissolution profiles of NDP were used to study the effect of the addition of polysorbate based on hydrophilic properties. A solid solution of NDP and AMCP was recently developed; however, the dissolution of NDP was <70%. In the present study, polysorbate was added to improve the dissolution of the drug by altering its hydrophilicity. The suitable formulation contained NDP and AMCP at a ratio of 1:4 and polysorbate at a concentration of 0.1%, 0.3%, or 0.6%. Differential scanning calorimetry and powder X-ray diffraction were used to examine the solid solutions. No peak representing crystalline NDP was observed in any solid solution samples, suggesting that the drug was molecularly dispersed in AMCP. The NDP dissolution from NDP powder and solid solution without PS were 16.82% and 58.19%, respectively. The highest dissolution of NDP of approximately 95.25% was noted at 120 min for the formulation containing 0.6% PS20. Linear correlations were observed between the surface free energy and percentages of dissolved NDP (R2 = 0.7115–0.9315). Cellular uptake across Caco-2 was selected to determine the drug permeability. The percentages of cellular uptake from the NDP powder, solid solution without and with PS20 were 0.25%, 3.60%, and 7.27%, respectively.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improvement in Solubility and Absorption of Nifedipine Using Solid Solution: Correlations between Surface Free Energy and Drug Dissolution

Tubtimsri

Weerapol

2021

Polymers

View full text Add to dashboard Cite

show abstract

“…In the absence of API recrystallization in the dissolution media, the degree of supersaturation appears to be dependent on the degree of vinyl pyrrolidone substitution. This dependency on vinyl pyrrolidone content for ketoprofen dissolution is an interesting observation which may be explained by the concept of congruent dissolution of drug and polymer, which is known to be aided by the presence of intermolecular interactions [40,41]. This argument is strengthened by the evidence of hydrogen bonding between PVP and ketoprofen which has been provided by the FTIR data.…”

Section: Influence Of Polymer Choice On Dynamic Solubilitymentioning

confidence: 73%

Physicochemical Properties of Poly-vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study

2020

View full text Add to dashboard Cite

When developing an amorphous solid dispersion (ASD), a prudent choice of polymer is critical to several aspects of ASD performance including: processability, solid state stability and dissolution rate. However, there is little guidance available to formulators to aid judicious polymer selection and a “trial and error” approach is often taken. This study aims to facilitate rational polymer selection and formulation design by generating ASDs using a range of poly-vinyl polymers and ketoprofen as a model active pharmaceutical ingredient (API) and evaluating several aspects of their performance. The molecular weight of the polymer and the ratio of vinyl pyrrolidone to vinyl acetate in the polymer were found to influence the relative humidity at which the relative humidity induced glass transition occurred, as well as the extent of ketoprofen supersaturation achieved during dynamic solubility testing. Interestingly, ASD tablets containing polymers with the vinyl pyrrolidone functional group exhibited higher tensile strengths than those without. This points towards the binder functionality of vinyl pyrrolidone. In conclusion, the physicochemical properties of poly-vinyl polymers greatly influence ketoprofen ASD performance and due regard should be paid to these properties in order to develop an ASD with the desired attributes.

show abstract

“…Therefore, a membrane permeability study in the well-established epithelial cellular models will be investigated in our further research. Furthermore, utilizing fast-dissolving excipients as carriers is an effective way to enhance drug dissolution [45]. The solubility of LM in water was significantly higher than that of MCC, which might result in higher bioavailability in vivo.…”

Section: Discussionmentioning

confidence: 99%

Combining Co-Amorphous-Based Spray Drying with Inert Carriers to Achieve Improved Bioavailability and Excellent Downstream Manufacturability

Zhang

Gao

et al. 2020

Pharmaceutics

View full text Add to dashboard Cite

It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.

show abstract

Mechanism of Enhanced Nifedipine Dissolution by Polymer-Blended Solid Dispersion through Molecular-Level Characterization

Cited by 29 publications

References 42 publications

Improvement in Solubility and Absorption of Nifedipine Using Solid Solution: Correlations between Surface Free Energy and Drug Dissolution

Improvement in Solubility and Absorption of Nifedipine Using Solid Solution: Correlations between Surface Free Energy and Drug Dissolution

Physicochemical Properties of Poly-vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study

Combining Co-Amorphous-Based Spray Drying with Inert Carriers to Achieve Improved Bioavailability and Excellent Downstream Manufacturability

Contact Info

Product

Resources

About