Complex amorphous solid dispersions based on poly(2-hydroxyethyl methacrylate): Study of drug release from a hydrophilic insoluble polymeric carrier in the presence and absence of a porosity increasing agent

Everaerts, Melissa; Mooter, Guy Van den

doi:10.1016/j.ijpharm.2019.05.040

Cited by 11 publications

(11 citation statements)

References 41 publications

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“…Previous studies have used various types of excipients to stabilize supersaturated system dynamics against recrystallization. 43 For supersaturated systems, the ideal carrier should dissolve quickly to produce a sufficiently high drug concentration and effectively maintain the supersaturated concentration. 44 As shown in Figure 5A, the solubility of Dio and PM was lower than the detection limit, so the value was recorded as 0.…”

Section: Aqueous Solubility and Dissolution Of Dio-asd Formulationsmentioning

confidence: 99%

<p>Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability</p>

Liu¹,

Zhou²,

Chang³

et al. 2020

DDDT

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Background and Purpose The traditional Chinese medicine, diosgenin (Dio), has attracted increasing attention because it possesses various therapeutic effects, including anti-tumor, anti-infective and anti-allergic properties. However, the commercial application of Dio is limited by its extremely low aqueous solubility and inferior bioavailability in vivo. Soluplus, a novel excipient, has great solubilization and capacity of crystallization inhibition. The purpose of this study was to prepare Soluplus-mediated Dio amorphous solid dispersions (ASDs) to improve its solubility, bioavailability and stability. Methods The crystallization inhibition studies were firstly carried out to select excipients using a solvent shift method. According to solubility and dissolution results, the preparation methods and the ratios of drug to excipient were further optimized. The interaction between Dio and Soluplus was characterized by differential scanning calorimetry (DSC), fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and molecular docking. The pharmacokinetic study was conducted to explore the potential of Dio ASDs for oral administration. Furthermore, the long-term stability of Dio ASDs was also investigated. Results Soluplus was preliminarily selected from various excipients because of its potential to improve solubility and stability. The optimized ASDs significantly improved the aqueous solubility of Dio due to its amorphization and the molecular interactions between Dio and Soluplus, as evidenced by dissolution test in vitro, DSC, FT-IR spectroscopy, SEM, PXRD and molecular docking technique. Furthermore, pharmacokinetic studies in rats revealed that the bioavailability of Dio from ASDs was improved about 5 times. In addition, Dio ASDs were stable when stored at 40°C and 75% humidity for 6 months. Conclusion These results indicated that Dio ASDs, with its high solubility, high bioavailability and high stability, would open a promising way in pharmaceutical applications.

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Section: Aqueous Solubility and Dissolution Of Dio-asd Formulationsmentioning

confidence: 99%

<p>Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability</p>

Liu¹,

Zhou²,

Chang³

et al. 2020

DDDT

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“…As the carrier will not dissolve, drug release is based on diffusion, creating a more steady increase in drug concentration and thus reducing the risk of precipitation [ 8 ]. Since drug release is based on diffusion, initial porosity of the formulation, possible changes in this property and the formation of physical crosslinks can affect the drug release and can, therefore, lead to insufficient drug release as previously demonstrated by our research group [ 9 ].…”

Section: Introductionmentioning

confidence: 93%

Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions

et al. 2020

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Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer’s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs.

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“…This study was carried out in order to indicate the presence of any interference which may be raised from the investigated carriers on the maximum absorbance of the drug in the used dilution range [36]. So, A 1% solution of each polymer in distilled water was scanned in the presence and absence of the drug using distilled water as a blank.…”

Section: Differential Ultraviolet Absorption Studymentioning

confidence: 99%

Utilization of Co-evaporation Technique for Enhancement the Solubility and Dissolution Rate of Etodolac

2021

J Pharmacol Pharm Res

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Etodolac (ETD), a member of non-steroidal anti-inflammatory drugs (NSAIDs), has a poor aqueous solubility. Long term administration of ETD causes severe gastrointestinal disturbances such as peptic ulcer and bleeding. The enhancement of its solubility and dissolution profile is expected to improve its bioavailability and reduce its side effects. In the present study, we tried to enhance the aqueous solubility and dissolution rate of ETD by two co-evaporation techniques. The first one is the formation of solid dispersion with different hydrophilic carriers, including polyethelene glycol (PEG 4000), polyvinyl pyrrolidones (PVP K25 and PVP K90) and urea. The second method is the formation of solid adsorbates using inert carriers such as avecil PH 101, bentonite and aerosil 200 as adsorbents. Co-evaporates were prepared at (1:1 w/w), (1:3 w/w) and (1:5 w/w) ETD to carrier ratios and the corresponding physical mixtures were also prepared. The solubility and dissolution studies of all formulations were measured. Moreover, the physicochemical properties of the modified co-evaporates were characterized using different techniques including, differential scanning calorimetry (DSC), infrared spectroscopy and X-ray diffractometry (XRD) analysis. The results showed that the co-evaporates exhibited higher dissolution rate than the corresponding physical mixtures and both showed higher dissolution rate than the unmodified drug. Increase polymer concentration led to increase in the dissolution rate of drug. Plus, the dissolution rate was enhanced by increasing the temperature of the dissolution medium. Avecil PH 101 exhibited the highest dissolution rate over all other polymers. Infrared studies showed no interaction between the drug and the investigated carrier. The DSC and XRD studies indicated the conversion of ETD to an amorphous state. The enhancement of the drug solubility may be attributed to the increase of drug surface area, the wettability, formation of hydrogen bonds and the conversion to amorphous state.

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Complex amorphous solid dispersions based on poly(2-hydroxyethyl methacrylate): Study of drug release from a hydrophilic insoluble polymeric carrier in the presence and absence of a porosity increasing agent

Cited by 11 publications

References 41 publications

<p>Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability</p>

<p>Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability</p>

Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions

Utilization of Co-evaporation Technique for Enhancement the Solubility and Dissolution Rate of Etodolac

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