scholarly journals Combining Co-Amorphous-Based Spray Drying with Inert Carriers to Achieve Improved Bioavailability and Excellent Downstream Manufacturability

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1063
Author(s):  
Yingxi Zhang ◽  
Yuan Gao ◽  
Xiaoxiao Du ◽  
Rou Guan ◽  
Zhonggui He ◽  
...  
Keyword(s):  
Spray Drying ◽  
Amorphous Solid ◽  
Relative Bioavailability ◽  
Pharmaceutical Product ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Therapeutic Drug ◽  
Lactose Monohydrate ◽  
Inert Carrier ◽  
Amorphous Formulation

It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.

scholarly journals Preparation and Characterization of Artemether Solid Dispersion by Spray Drying Technique

2021 ◽  
Vol 11 (2) ◽  
pp. 1-5
Author(s):  
Dhiraj Dabhade ◽  
Kamlesh Wadher ◽  
Shrikant Bute ◽  
Nikita Naidu ◽  
Milind Umekar ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Spray Drying ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Study Data ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Poorly Water Soluble

Introduction: Artemether, a BCS class IV drug (poorly water soluble and poorly permeable, less bioavailability) but is found to be effective against falciparum malaria. Preparation of water soluble formulation could be the technique to improve bioavailability of such drug. The most ideally used technique to enhance the solubility and dissolution of poorly water soluble drugs is Solid dispersion method. Method: The objective of the study was to enhance the solubility and dissolution rate of Artemether by preparing solid dispersions using Soluplus, at different ration of 1:1, 1:2, 1:3 and 1:4 using spray drying technology. Prepared Solid dispersions were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The spray-dried solid dispersions found to be having less crystallinity and showed higher dissolution rates. Solubility study data showed the optimum drug/Soluplus ratio to be 1:3. The dissolution studies of Solid dispersions in 1.2 pH and 6.8 pH buffer showed higher drug release as compared to pure drug. Conclusion: Thus we conclude that an amorphous solid dispersion of Artemether could be a better option for enhancing the dissolution rate of drug Keywords: solid dispersion, artemether, soluplus, solubility enhancement

scholarly journals Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 889
Author(s):  
Kaijie Qian ◽  
Lorenzo Stella ◽  
David S. Jones ◽  
Gavin P. Andrews ◽  
Huachuan Du ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Nucleation Theory ◽  
Product Development Process ◽  
Classical Nucleation Theory ◽  
Oral Drug ◽  
Amorphous Solid Dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

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 Silymarin-solid dispersions: Characterization and influence of preparation methods on dissolution

2010 ◽  
Vol 60 (4) ◽  
pp. 427-443 ◽  
Author(s):  
Dalwadi Sonali ◽  
Soni Tejal ◽  
Thakkar Vaishali ◽  
Gandhi Tejal
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Precipitation Method ◽  
Amorphous Solid Dispersion ◽  
Preparation Methods ◽  
Hydrogen Bond Formation ◽  
Pure Drug ◽  
Co Precipitation

Silymarin-solid dispersions: Characterization and influence of preparation methods on dissolution The influence of preparation methodology of silymarin solid dispersions using a hydrophilic polymer on the dissolution performance of silymarin was investigated. Silymarin solid dispersions were prepared using HPMC E 15LV by kneading, spray drying and co-precipitation methods and characterized by FTIR, DSC, XRPD and SEM. Dissolution profiles were compared by statistical and model independent methods. The FTIR and DSC studies revealed weak hydrogen bond formation between the drug and polymer, while XRPD and SEM confirmed the amorphous nature of the drug in co-precipitated solid dispersion. Enhanced dissolution compared to pure drug was found in the following order: co-precipitation > spray drying > kneading methodology (p < 0.05). All preparation methods enhanced silymarin dissolution from solid dispersions of different characteristics. The co-precipitation method proved to be best and provided a stable amorphous solid dispersion with 2.5 improved dissolution compared to the pure drug.

scholarly journals Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 353
Author(s):  
Hiroshi Ueda ◽  
Yuya Hirakawa ◽  
Hironori Tanaka ◽  
Tetsuya Miyano ◽  
Katsuji Sugita
Keyword(s):  
Solid Dispersion ◽  
Hydroxypropyl Methylcellulose ◽  
Principal Component ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Amorphous Drug

The transformation of a crystalline drug into an amorphous form is a promising way to enhance the oral bioavailability of poorly water-soluble drugs. Blending of a carrier, such as a hydrophilic polymer, with an amorphous drug is a widely used method to produce a solid dispersion and inhibit crystallization. This study investigates an experimental grade of hydroxypropyl methylcellulose acetate succinate, HPMCAS-MX (MX), as a solid dispersion carrier. Enhancement of thermal stability and reduction of the glass transition temperature (Tg) of MX compared with those of the conventional grade were evaluated through thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of a homogeneous amorphous solid dispersion between MX and indomethacin was confirmed by X-ray powder diffraction analysis, DSC, and Raman mapping. It was observed that 10–30% MX did not act as an anti-plasticizer, but the utilization of >40% MX caused an increase in Tg and reduction of molecular mobility. This could be explained by a change in intermolecular interactions, inferred from infrared spectroscopy combined with principal component analysis. HPMCAS-MX exhibited similar performance to that of conventional-grade, HPMCAS-MG. Although HPMCAS-MX has thermal properties different from those of conventional-grade HPMCAS-MG, it retains its ability as a solid dispersion carrier.

scholarly journals In Vitro-In Silico Tools for Streamlined Development of Acalabrutinib Amorphous Solid Dispersion Tablets

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1257
Author(s):  
Deanna M. Mudie ◽  
Aaron M. Stewart ◽  
Jesus A. Rosales ◽  
Molly S. Adam ◽  
Michael M. Morgen ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
In Silico ◽  
Ph Effect ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous Solid ◽  
Dosage Forms ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
In Silico Tools

Amorphous solid dispersion (ASD) dosage forms can improve the oral bioavailability of poorly water-soluble drugs, enabling the commercialization of new chemical entities and improving the efficacy and patient compliance of existing drugs. However, the development of robust, high-performing ASD dosage forms can be challenging, often requiring multiple formulation iterations, long timelines, and high cost. In a previous study, acalabrutinib/hydroxypropyl methylcellulose acetate succinate (HPMCAS)-H grade ASD tablets were shown to overcome the pH effect of commercially marketed Calquence in beagle dogs. This study describes the streamlined in vitro and in silico approach used to develop those ASD tablets. HPMCAS-H and -M grade polymers provided the longest acalabrutinib supersaturation sustainment in an initial screening study, and HPMCAS-H grade ASDs provided the highest in vitro area under the curve (AUC) in gastric to intestinal transfer dissolution tests at elevated gastric pH. In silico simulations of the HPMCAS-H ASD tablet and Calquence capsule provided good in vivo study prediction accuracy using a bottom–up approach (absolute average fold error of AUC0-inf < 2 except for Calquence + famotidine ≈ 3). This streamlined approach combined an understanding of key drug, polymer, and gastrointestinal properties with in vitro and in silico tools to overcome the acalabrutinib pH effect without the need for reformulation or multiple studies, showing promise for reducing time and costs to develop ASD drug products.

Sign in / Sign up

Export Citation Format

Share Document