Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement

Nandi, Uttom; Ajiboye, Adejumoke Lara; Patel, Pritash; Douroumis, Dennis; Trivedi, Vivek

doi:10.3390/ph14090846

Cited by 30 publications

(29 citation statements)

References 54 publications

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“…Soluplus (SOL), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, is an amphiphilic polymer mainly used in solid dispersions. It not only displays superior solubilizing effects for Biopharmaceutics Classification System (BCS) class II drugs, but also forms micelles in aqueous solution, exhibiting better solubilization ability than conventional surfactants [ 23 ]. In addition, its surface activity is beneficial for maintaining the supersaturation of poorly soluble drugs in the gastrointestinal (GI) tract [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Stabilizing Effect of Soluplus on Erlotinib Metastable Crystal Form in Microparticles and Amorphous Solid Dispersions

et al. 2022

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Microparticles (MPs) and amorphous solid dispersions (SDs) are effective methods to improve the dissolution of insoluble drugs. However, stability is a concern for these two high-energy systems, resulting from high surface area and amorphous polymorph, respectively. As an amphiphilic polymer, Soluplus (SOL) is usually used as a carrier in SDs. In this study, erlotinib microparticles (ERL MPs) and erlotinib solid dispersions (ERL SDs) were prepared with SOL by bottom-up technology and solvent evaporation. The solid-state properties of ERL MPs and ERL SDs were characterized by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The ERL MPs existed in a metastable crystal form A while the ERL SDs existed in an amorphous state. Fourier transform infrared spectroscopy (FT-IR) showed that there was a hydrogen bond interaction between the N-H group of ERL and the carbonyl group of SOL in ERL MPs and SDs. The dissolution profiles of ERL SDs and ERL MPs were improved significantly. ERL MPs showed better stability than ERL SDs in accelerated stability test. The discrepant stabilizing effects of polymer SOL in two systems may provide effective ideas for solubilization of insoluble drugs and the stability of drugs after recrystallization.

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Section: Introductionmentioning

confidence: 99%

Stabilizing Effect of Soluplus on Erlotinib Metastable Crystal Form in Microparticles and Amorphous Solid Dispersions

et al. 2022

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“…According to data in the literature, Soluplus® showed peaks at 3448 cm −1 due to O–H stretching, at 2927 cm −1 due to aromatic C–H stretching, at 1735 cm −1 and 1635 cm −1 due to C=O stretching, and at 1477 cm −1 due to C–O–C stretching. All these peaks are observed in the FTIR spectra of studied solid dispersions which contain Soluplus ® (SD7–SD11) [ 49 , 50 ].…”

Section: Resultsmentioning

confidence: 99%

“…The XRD patterns of solid dispersions are shown in Figure 7 . From the literature, the diffractogram of Soluplus® displayed no peaks due to its amorphous nature [ 50 ]. The poloxamer 188 presented two peaks at 19.3 and the other broader one between 22° and 23° [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

The Influence of the Polymer Type on the Quality of Newly Developed Oral Immediate-Release Tablets Containing Amiodarone Solid Dispersions Obtained by Hot-Melt Extrusion

et al. 2022

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The present study aims to demonstrate the influence of the polymer-carrier type and proportion on the quality performance of newly developed oral immediate-release tablets containing amiodarone solid dispersions obtained by hot-melt extrusion. Twelve solid dispersions including amiodarone and different polymers (PEG 1500, PEG 4000; PEG 8000, Soluplus®, and Kolliphor® 188) were developed and prepared by hot-melt extrusion using a horizontal extruder realized by the authors in their own laboratory. Only eleven of the dispersions presented suitable physical characteristics and they were used as active ingredients in eleven tablet formulations that contain the same amounts of the same excipients, varying only in solid dispersion type. The solid dispersions’ properties were established by optical microscopy with reflected light, volumetric controls and particle size evaluation. In order to prove that the complex powders have appropriate physical characteristics for the direct compression process, they were subjected to different analyses regarding their flowability and compressibility behavior. Additionally, the Fourier transform infrared spectroscopy and X-ray diffraction analysis were performed on the obtained solid dispersions. After confirming the proper physical attributes for all blends, they were processed into the form of tablets by direct compression technology. The manufactured tablets were evaluated for pharmacotechnical (dimensions–diameter and thickness, mass uniformity, hardness and friability) and in vitro biopharmaceutical (disintegration time and drug release) performances. Furthermore, the influence of the polymer matrix on their quality was determined. The high differences in flow and compression performances of the solid dispersions prove the relevant influence of the polymer type and their concentration-dependent plasticizing properties. The increase in flowability and compressibility characteristics of the solid dispersions could be noticed after combining them with direct compression excipients owning superior mechanical qualities. The influence of the polymer type is best detected in the disintegration test, where the obtained values are quite different between the studied formulations. The use of PEG 1500 alone or combined in various proportions with Soluplus® leads to rapid disintegration. In contrast, the mixture of PEG 4000 and Poloxamer 188 in equal proportions determined the increase in disintegration time to 120 s. The use of Poloxamer 188 alone and a 3:1 combination of PEG 4000 and Soluplus® also generates a prolonged disintegration time for the tablets.

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“…Because of this, bypassing the liver metabolism and improving the solubility of pitavastatin is an attractive approach to enhancing its therapeutic effect. Different approaches have been taken for the delivery of poorly soluble drugs, e.g., solid dispersion, particle size reduction, co-precipitation, and lipid-based drug delivery systems [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the Solubility and Bioavailability of Pitavastatin through a Self-Nanoemulsifying Drug Delivery System (SNEDDS)

et al. 2022

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The purpose of the study was to develop an SNEDDS to improve the solubility and bioavailability of pitavastatin. The solubility of pitavastatin in different oils, surfactants, and co-surfactants was determined and a pseudo-ternary phase diagram was constructed. The SNEDDS was characterized by zeta-sizer, zeta-potential, FTIR, DSC, and TGA. Release and permeation of pitavastatin from the SNEDDS was studied for 12 and 24 h, respectively. The lipolysis test, RBC lysis, effect on lipid profile, and pharmacokinetics were studied. The SPC3 formulation showed a 104 ± 1.50 nm particle size, a 0.198 polydispersity index (PDI), and a –29 zeta potential. FTIR, DSC, and TGA showed the chemical compatibility and thermal stability. The release and permeation of pitavastatin from SPC3 was 88.5 ± 2.5% and 96%, respectively. In the lipolysis test, the digestion of SPC3 yielded a high amount of pitavastatin and showed little RBC lysis. The lipid profile suggested that after 35 days of administration of the SNEDDS, there was a marked decrease in TC, LDL, and triglyceride levels. The SNEDDS of SPC3 showed an 86% viability of Caco-2 cells. Pharmacokinetics of SPC3 showed improved values of Cmax, Tmax, half-life, MRT, AUC, and AUMC compared to the reference formulation. Our study demonstrated that the SNEDDS effectively enhanced the solubility and bioavailability of a BCS class II drug.

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Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement

Cited by 30 publications

References 54 publications

Stabilizing Effect of Soluplus on Erlotinib Metastable Crystal Form in Microparticles and Amorphous Solid Dispersions

Stabilizing Effect of Soluplus on Erlotinib Metastable Crystal Form in Microparticles and Amorphous Solid Dispersions

The Influence of the Polymer Type on the Quality of Newly Developed Oral Immediate-Release Tablets Containing Amiodarone Solid Dispersions Obtained by Hot-Melt Extrusion

Enhancement of the Solubility and Bioavailability of Pitavastatin through a Self-Nanoemulsifying Drug Delivery System (SNEDDS)

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