Investigation of Atypical Dissolution Behavior of an Encapsulated Amorphous Solid Dispersion

Puri, Vibha; Dantuluri, Ajay K.; Bansal, Arvind K.

doi:10.1002/jps.22462

Cited by 26 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In both stud-698 ies the dose of Td released from the Td/HPMC system was lower 699 than that released from the capsule containing crystalline Td. The 700 delayed release of a drug from a solid dispersion after its encap-701 sulation without disintegrants, when compared to the free pow-702 der, has been already described by Puri et al [17]. In the study of 703 Puri the fill of the capsule formed a plug, which remained undis- …”

mentioning

confidence: 84%

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

Wlodarski

Sawicki

Haber

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

mentioning

confidence: 84%

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

Wlodarski

Sawicki

Haber

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

“…However, to develop a commercial dosage form the solid dispersion needs to be converted to a final dosage form such as tablets or capsules. It has been observed that when solid dispersions are filled into capsules or compressed into tablets, the disintegration time might be too long (>30 min) due to formation of non-dispersible plug, which results in incomplete or non-optimal drug release (14)(15)(16). Polymers are major component in most of the amorphous solid dispersions as the typical drug loading is in the range of 10-50%.…”

Section: Introductionmentioning

confidence: 99%

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

et al. 2016

View full text Add to dashboard Cite

ABSTRACT. The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus-and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

show abstract

“…Due to the high energy state of such nanoparticles, however, maintaining their state of dispersion requires stabilization, which can be achieved, e.g. , either by adsorbing a stabilizing surfactant or polymer layer on the nanoparticle surface, or by embedding the nanoparticles in a matrix, thus being equivalent to solid dispersions in the microscale (3–5). …”

Section: Introductionmentioning

confidence: 99%

Carbon Dioxide-Mediated Generation of Hybrid Nanoparticles for Improved Bioavailability of Protein Kinase Inhibitors

et al. 2013

View full text Add to dashboard Cite

PurposeA versatile methodology is demonstrated for improving dissolution kinetics, gastrointestinal (GI) absorption, and bioavailability of protein kinase inhibitors (PKIs).MethodsThe approach is based on nanoparticle precipitation by sub- or supercritical CO2 together with a matrix-forming polymer, incorporating surfactants either during or after nanoparticle formation. Notably, striking synergistic effects between hybrid PKI/polymer nanoparticles and surfactant added after particle formation is investigated.ResultsThe hybrid nanoparticles, consisting of amorphous PKI embedded in a polymer matrix (also after 12 months), display dramatically increased release rate of nilotinib in both simulated gastric fluid and simulated intestinal fluid, particularly when surfactants are present on the hybrid nanoparticle surface. Similar results indicated flexibility of the approach regarding polymer identity, drug load, and choice of surfactant. The translation of the increased dissolution rate found in vitro into improved GI absorption and bioavalilability in vivo was demonstrated for male beagle dogs, where a 730% increase in the AUC0–24h was observed compared to the benchmark formulation. Finally, the generality of the formulation approach taken was demonstrated for a range of PKIs.ConclusionsHybrid nanoparticles combined with surfactant represent a promising approach for improving PKI dissolution rate, providing increased GI absorption and bioavailability following oral administration.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-013-1191-4) contains supplementary material, which is available to authorized users.

show abstract

Investigation of Atypical Dissolution Behavior of an Encapsulated Amorphous Solid Dispersion

Cited by 26 publications

References 31 publications

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

Carbon Dioxide-Mediated Generation of Hybrid Nanoparticles for Improved Bioavailability of Protein Kinase Inhibitors

Contact Info

Product

Resources

About