In vitro-in silico evaluation of Apremilast solid dispersions prepared via Corotating Twin Screw Extruder

Muvva, Aneesh; Lakshman, Dani; Dwibhashyam, V. S. N. Murthy; Dengale, Swapnil J.; Lewis, Shaila

doi:10.1016/j.jddst.2020.101844

Cited by 10 publications

(3 citation statements)

References 37 publications

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“…The ASDs improve drug solubility through different mechanisms, either in combination or alone, including amorphization, wettability, particle size reduction, inhibition of drug recrystallization, and intermolecular interactions [ 17 , 18 ]. Furthermore, in the preparation of ASDs, techniques such as hot-melt extrusion [ 19 ], spray drying [ 20 ], quench cooling [ 21 ], solvent evaporation [ 22 ], and freeze-drying [ 23 ] were widely utilized. Amorphous salt solid dispersion (ASSD) is a new approach that combines the advantages of amorphization and salt formation to improve the physical stability, aqueous solubility, and dissolution rate of the drug in an amorphous form.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

Yarlagadda

Nayak

Brahmam

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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Amorphous salt solid dispersion (ASSD) of Dolutegravir amorphous salt (DSSD) was generated using quench cooling and compared to its Dolutegravir free acid solid dispersion (DFSD) to improve the solubility and bioavailability. Soluplus (SLP) was used as a polymeric carrier in both solid dispersions. The prepared DSSD and DFSD, physical mixtures, and individual compounds were characterized by employing DSC, XRPD, and FTIR to assess the formation of the single homogenous amorphous phase and the existence of intermolecular interactions. Partial crystallinity was observed for DSSD, unlike DFSD, which is completely amorphous. No intermolecular interactions were observed between the Dolutegravir sodium (DS)/Dolutegravir free acid (DF) and SLP from the FTIR spectra of DSSD and DFSD. Both DSSD and DFSD improved the solubility of Dolutegravir (DTG) to 5.7 and 4.54 folds compared to the pure forms. Similarly, drug release from DSSD and DFSD was 2 and 1.5 folds higher than that in the pure form, owing to the rapid dissolution of the drug from the formulations. The permeability of DSSD and DFSD was estimated using the dialysis membrane, which enhanced the DTG permeability. The improvement in in vitro studies was translated into in vivo pharmacokinetic profiles of DSSD and DFSD, where 4.0 and 5.6 folds, respectively, improved the Cmax of DTG.

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Section: Introductionmentioning

confidence: 99%

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

Yarlagadda

Nayak

Brahmam

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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“…14 ASDs improve drug solubility through multiple mechanisms, including wettability, particle size reduction, intermolecular interactions, and amorphization. 15,16 Further, spray drying, 17 hot-melt extrusion, 18 freeze drying, 19 quench cooling, 20 and solvent evaporation 21 were widely used techniques to prepare ASDs. Amorphous Salt Solid Dispersion (ASSD) is a novel strategy that combines the advantages of amorphization and salt formation to improve amorphous drug physical stability, aqueous solubility, and dissolution rate.…”

Section: Introductionmentioning

confidence: 99%

Solid State Characterization and Miscibility of Raltegravir in Soluplus Using Solid Dispersion Technology

Yarlagadda,

Nayak,

Bhat

2023

Ind. J. Pharm. Edu. Res.

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Background: Raltegravir Potassium (RTGP), a BCS class II drug used in the treatment of HIV, has minimal solubility in the aqueous medium, resulting in poor bioavailability; Further, RTGP poor dissolution and limited solubility are also major factors responsible for the significant inter-and intra-patient variability in absorption following oral administration. Objectives: To enhance the solubility of Raltegravir potassium and its free acid using Soluplus ® by solid dispersion technology. Materials and Methods: In the current study, Amorphous Solid Dispersions (ASDs) of RTGP and Raltegravir free acid (RTG) of 20:80% w/w with Soluplus ® (SLP) were prepared using quench cooling. The prepared ASDs analyzed for homogenous single-phase formation and intermolecular interactions employing DSC, XRD, and FT-IR. The drug-polymer miscibility was calculated theoretically as well as experimentally with the aid of Hansen solubility parameter and melting point depression methods. The solubility of the ASDs was evaluated by the shake flask method. Results: Quench cooling yielded an RTGP-SLP and RTG-SLP homogeneous amorphous systems. DSC and XRPD results showed the complete transformation of crystalline to the amorphous phase for ASDs. Intermolecular interactions in specific hydrogen bonding were observed between the carbonyl (-C=O) group of Soluplus ® and the Raltegravir -N-H moiety. RTG solubility in salt solid dispersion increases by 10.7 and 17.4 folds, respectively, compared to pure forms. Furthermore, free acid ASDs improved solubility by 8.7 and 14.1 folds, respectively, compared to their pure compounds. Conclusion: Salt solid dispersion showed a greater extent of miscibility and improved solubility of RTG compared to free acid solid dispersion.

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“…This drug causes an intracellular accumulation of cyclic adenosine monophosphate (cAMP), resulting in a modification in the signaling pathways of cells belonging to the innate (monocytes) and adaptive (T cells) immune system as well as non-immune cells (keratinocytes) [ 11 , 12 ]. In the last decade, novel drug delivery systems for APR has been reported in order to improve its solubility and bioavailability including PLGA nanoparticles [ 13 ], amorphous solid dispersion [ 14 ], nanostructured lipid carriers [ 15 ] and nanocrystal-based formulations [ 16 ]. Currently, APR is available in tablet form of 10, 20 and 30 mg for oral administration [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation

et al. 2020

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Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.

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In vitro-in silico evaluation of Apremilast solid dispersions prepared via Corotating Twin Screw Extruder

Cited by 10 publications

References 37 publications

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

Solid State Characterization and Miscibility of Raltegravir in Soluplus Using Solid Dispersion Technology

Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation

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