scholarly journals Amorphous Solid Dispersions and the Contribution of Nanoparticles to In Vitro Dissolution and In Vivo Testing: Niclosamide as a Case Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 97 ◽  
Author(s):  
Miguel O. Jara ◽  
Zachary N. Warnken ◽  
Robert O. Williams
Keyword(s):  
Amorphous Solid ◽  
Fold Increase ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
In Vitro Tests ◽  
Scanning Calorimetry ◽  
Poorly Water Soluble

We developed an amorphous solid dispersion (ASD) of the poorly water-soluble molecule niclosamide that achieved a more than two-fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60-fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, Biopharmaceutics Classification System (BCS) class II, and a poor glass former with low bioavailability in vivo. Hot-melt extrusion is a high-throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP–VA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and dynamic light scattering (DLS). The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side-by-side diffusion test, these nanoparticles produced a four-fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

scholarly journals Amorphous solid dispersions and the confounding effect of nanoparticles in in vitro dissolution and in vivo testing: Niclosamide as a case of study

2020 ◽  
Author(s):  
Miguel O Jara ◽  
Zachary N Warnken ◽  
Robert O Williams
Keyword(s):  
Amorphous Solid ◽  
Fold Increase ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
In Vitro Tests ◽  
Manufacturing Method ◽  
Poorly Water Soluble

We developed an amorphous solid dispersion (ASD) of the poorly water soluble molecule niclosamide that achieved more than a 2 fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60 fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, BCS class II, and a poor glass former with low bioavailability in vivo. Hot melt extrusion is a high throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer polyvinylpyrrolidone vinyl acetate (PVPVA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using DSC, XRD, NMR, FTIR, and DLS. The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side by side diffusion test, these nanoparticles produced a 4 fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

scholarly journals Amorphous Solid Dispersions and the Confounding Effect of Nanoparticles in in Vitro Dissolution and in Vivo Testing: Niclosamide as a Case Study

2020 ◽  
Author(s):  
Robert Williams III ◽  
Zachary Warnken ◽  
Miguel Jara
Keyword(s):  
Amorphous Solid ◽  
Fold Increase ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
In Vitro Tests ◽  
Manufacturing Method ◽  
Poorly Water Soluble

We developed an amorphous solid dispersion (ASD) of the poorly water-soluble molecule niclosamide that achieved more than a 2-fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60-fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, BCS class II, and a poor glass former with low bioavailability in vivo. Hot-melt extrusion is a high-throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer polyvinylpyrrolidone–vinyl acetate (PVP–VA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using DSC, XRD, NMR, FTIR, and DLS. The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side-by-side diffusion test, these nanoparticles produced a 4-fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

scholarly journals Improved Dissolution and Pharmacokinetics of Abiraterone through KinetiSol® Enabled Amorphous Solid Dispersions

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 357 ◽  
Author(s):  
Urvi Gala ◽  
Dave Miller ◽  
Robert O. Williams
Keyword(s):  
Amorphous Solid ◽  
High Energy ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Dissolution Enhancement ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Simulated Intestinal Fluid ◽  
Modulated Differential Scanning Calorimetry

Abiraterone is a poorly water-soluble drug. It has a high melting point and limited solubility in organic solvents, making it difficult to formulate as an amorphous solid dispersion (ASD) with conventional technologies. KinetiSol® is a high-energy, fusion-based, solvent-free technology that can produce ASDs. The aim of this study was to evaluate the application of KinetiSol to make abiraterone ASDs. We developed binary KinetiSol ASDs (KSDs) using both polymers and oligomers. For the first time, we reported that KinetiSol can process hydroxypropyl-β-cyclodextrin (HPBCD), a low molecular-weight oligomer. Upon X-ray diffractometry and modulated differential scanning calorimetry analysis, we found the KSDs to be amorphous. In vitro dissolution analysis revealed that maximum abiraterone dissolution enhancement was achieved using a HPBCD binary KSD. However, the KSD showed significant abiraterone precipitation in fasted state simulated intestinal fluid (FaSSIF) media. Hence, hypromellose acetate succinate (HPMCAS126G) was selected as an abiraterone precipitation inhibitor and an optimized ternary KSD was developed. A pharmacokinetic study revealed that HPBCD based binary and ternary KSDs enhanced abiraterone bioavailability by 12.4-fold and 13.8-fold, respectively, compared to a generic abiraterone acetate tablet. Thus, this study is the first to demonstrate the successful production of an abiraterone ASD that exhibited enhanced dissolution and bioavailability.

DEVELOPMENT AND EVALUATION OF ZIPRASIDONE LOADED SOLID SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (08) ◽  
pp. 53-60
Author(s):  
Purushottam Patil ◽  
Malik Shaikh ◽  
Paresh Mahaparale
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Physical Adsorption ◽  
Gastrointestinal Transit ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Poorly Water Soluble

Solid self-micro emulsification technique is the new approach for poorly water-soluble and poorly bioavailable drugs by allowing the drug substance to be incorporated into the oil phase and thus having the ability to permeate the GI membrane to a faster extent. Oleic acid, Tween 80, methanol and colloidal silicon dioxide were used as penetrant, surfactant, co-surfactant and adsorbent, respectively. The interaction between drug and excipients was examined by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The results of DSC and FTIR studies did not reveal any possible drug-excipient interactions. The conversion of liquid self-microemulsifying drug delivery system (SMEDDS) into the solid SMEDDS increases the stability of the emulsion formulation achieved by physical adsorption of an adsorbent material. The release of drug from SMEDDS formulation is justified by in-vitro dissolution studies. SMEDDS increases the solubility of the drug and improves the bioavailability, without disturbing gastrointestinal transit. SMEDDS has the potential to provide a useful oral solid dosage form for the poorly water-soluble drug ziprasidone.

scholarly journals Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 235 ◽  
Author(s):  
Lyes Mehenni ◽  
Malika Lahiani-Skiba ◽  
Guy Ladam ◽  
François Hallouard ◽  
Mohamed Skiba
Keyword(s):  
Amphotericin B ◽  
Solid Dispersion ◽  
In Vitro Release ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
New Generation ◽  
Powder Aerosols

In the present study, new polymer microspheres of amphotericin B (AmB) were prepared by a spray drying technique using cyclodextrin polymers (Poly-CD) to improve the solubility and dissolution of AmB, to prevent in vivo toxic AmB aggregations. Formulations were characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermal analysis, Raman spectroscopy, particle size, drug purity test and in vitro release studies. The analysis indicated that the chemical structure of AmB remained unchanged in the amorphous solid dispersion, but the structure was changed from crystalline to amorphous. AmB was completely release from such optimized formulations in dissolution media in 40 min. This work may contribute to a new generation of spherical amorphous solid dispersion using a cyclodextrin polymer, which has implications for the possibility of drug development for oral utilization or as powder aerosols for pulmonary administration.

Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier

2017 ◽  
Vol 531 (1) ◽  
pp. 324-331 ◽  
Author(s):  
Johan Wendelboe ◽  
Matthias Manne Knopp ◽  
Fauzan Khan ◽  
Nabil Chourak ◽  
Thomas Rades ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Ph Sensitive ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion
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