Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

Karagianni, Anna; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

doi:10.3390/pharmaceutics10030098

Cited by 156 publications

(109 citation statements)

References 102 publications

(216 reference statements)

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“…The review will cover polymeric carriers employed in binary solid dispersions; however, the discussion about small molecular weight carriers is out of the scope of this manuscript, as this space is assumed by so-called co-amorphous technology. The interested readers are advised to read many interesting reviews about co-amorphous technology ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

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Solid dispersion is the preferred technology to prepare efficacious forms of BCS class-II/IV APIs. To prepare solid dispersions, there exist a wide variety of polymeric carriers with interesting physicochemical and thermochemical characteristics available at the disposal of a formulation scientist. Since the advent of the solid dispersion technology in the early 1960s, there have been more than 5000 scientific papers published in the subject area. This review discusses the polymeric carrier properties of most extensively used polymers PVP, Copovidone, PEG, HPMC, HPMCAS, and Soluplus® in the solid dispersion technology. The literature trends about preparation techniques, dissolution, and stability improvement are analyzed from the Scopus® database to enable a formulator to make an informed choice of polymeric carrier. The stability and extent of dissolution improvement are largely dependent upon the type of polymeric carrier employed to formulate solid dispersions. With the increasing acceptance of transfer dissolution setup in the research community, it is required to evaluate the crystallization/precipitation inhibition potential of polymers under dynamic pH shift conditions. Further, there is a need to develop a regulatory framework which provides definition and complete classification along with necessarily recommended studies to characterize and evaluate solid dispersions.

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Section: Introductionmentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

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“…The solid states (polymorphs, salt, cocrystals, multicomponent crystals, crystallites, co-amorphous, and amorphous) of Active Pharmaceutical Ingredient (APIs) have a significant impact on the solubility and dissolution behavior of these APIs, and therefore alter the drug’s bioavailability. Therefore, several studies focusing on the design and development of methods for controlling the drug’s solid states have been actively conducted, recently [1,2,3,4,5].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of the Solution-Mediated Polymorphic Transformation of the Novel l-Carnitine Orotate Polymorph, Form-II

Youn

Kiyonga

et al. 2018

Pharmaceutics

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Research studies related to the polymorphs of l-Carnitine orotate (CO), a medication used for the treatment and prevention of liver diseases, are insignificant or almost nonexistent. Accordingly, in the present study, l-Carnitine orotate (CO) was prepared for investigating CO polymorphs. Here, a reactive crystallization was induced by reacting 1g of l-Carn (1 equivalent) and 0.97 g of OA (1 equivalent) in methanol (MeOH); as a result, CO form-I and CO form-II polymorphs were obtained after 1 h and 16 h of stirring, respectively. The characterization of CO polymorphs was carried out utilizing Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and solid-state Nuclear Magnetic Resonance Spectroscopy (solid-state CP/MAS 13C-NMR). The solution-mediated polymorphic transformation (SMPT) of CO polymorphs was investigated in MeOH at controlled temperature and fixed rotational speed. The results revealed that CO form-I is a metastable polymorph while CO form-II is a stable polymorph. From the same results, it was confirmed that CO form-I was converted to CO form-II during the polymorphic phase transformation process. Moreover, it was assessed that the increase in temperature and supersaturation level significantly promotes the rate of nucleation, as well as the rate of mass transfer of CO form-II. In addition, nucleation and mass transfer equations were employed for the quantitative determination of SMPT experimental results. Lastly, it was suggested that CO form-II was more thermodynamically stable than CO form-I and that both polymorphs belong to the monotropic system.

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“…Co-amorphous systems have gained interest as a promising system to stabilize poorly water-soluble drugs in an amorphous form over the last few years [ 1 ]. These co-amorphous systems are defined as mixtures between the active pharmaceutical ingredient (API) and one or more small molecular compounds, in order to differentiate them from polymeric glass solutions [ 2 ]. Although drug–drug combinations were originally the focus [ 3 , 4 ], this has changed as drug–excipient combinations result in more universally applicable systems.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Co-Amorphous Systems by Freeze-Drying

2020

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Freeze-drying was evaluated as a production technique for co-amorphous systems of a poorly water-soluble drug. Naproxen was freeze-dried together with arginine and lysine as co-former. To increase the solubility of naproxen in the starting solution, the applicability of five surfactants was investigated, namely sodium dodecyl sulfate, pluronic F-127, polyoxyethylene (40) stearate, tween 20 and TPGS 1000. The influence of the surfactant type, surfactant concentration and total solid content to be freeze-dried on the solid state of the sample was investigated. X-ray powder diffraction and differential scanning calorimetry showed that the majority of systems formed co-amorphous one-phase systems. However, at higher surfactant concentrations, and depending on the surfactant type, surfactant reflections were observed in the XRPD analysis upon production. Crystallization of both naproxen and amino acid occurred from some combinations under storage. In conclusion, freeze-drying was shown to be a feasible technique for the production of a selection of co-amorphous drug–amino acid formulations.

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Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

Cited by 156 publications

References 102 publications

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Kinetics of the Solution-Mediated Polymorphic Transformation of the Novel l-Carnitine Orotate Polymorph, Form-II

Preparation of Co-Amorphous Systems by Freeze-Drying

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