Predicting Spray Dried Dispersion Particle Size Via Machine Learning Regression Methods.

Spray dried dispersion particle size is a critical quality attribute that impacts bioavailability and manufacturability of the spray drying process and final dosage form. Substantial experimentation has been required to relate formulation and process parameters to particle size with the results limited to a single active pharmaceutical ingredient (API). This is the first study that demonstrates prediction of particle size independent of API for a wide range of formulation and process parameters at pilot and commercial scale.

Correction: Adam et al. Acetic Acid as Processing Aid Dramatically Improves Organic Solvent Solubility of Weakly Basic Drugs for Spray Dried Dispersion Manufacture. 2022, , 555.

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Acetic Acid as Processing Aid Dramatically Improves Organic Solvent Solubility of Weakly Basic Drugs for Spray Dried Dispersion Manufacture.

Many active pharmaceutical ingredients (APIs) in the pharmaceutical pipeline require bioavailability enhancing formulations due to very low aqueous solubility. Although spray dried dispersions (SDDs) have demonstrated broad utility in enhancing the bioavailability of such APIs by trapping them in a high-energy amorphous form, many new chemical entities (NCEs) are poorly soluble not just in water, but in preferred organic spray drying solvents, e.g.

Correction: Mudie et al. In Vitro-In Silico Tools for Streamlined Development of Acalabrutinib Amorphous Solid Dispersion Tablets. 2021, , 1257.

The authors wish to make the following corrections to this paper [...

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

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.

Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs.

Calquence (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug-drug interactions (DDIs) negatively impact patient treatment and quality of life due to the strict dosing regimens required. In this study, reduced plasma drug exposure at high gastric pH was overcome using a spray-dried amorphous solid dispersion (ASD) comprising 50% acalabrutinib and 50% hydroxypropyl methylcellulose acetate succinate (HPMCAS, H grade) formulated as an immediate-release (IR) tablet.

Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions.

Spray drying is widely used in the manufacturing of amorphous solid dispersion (ASD) systems due to its fast drying rate, enabling kinetic trapping of the drug in amorphous form. Spray-drying conditions, such as solvent composition, can have a profound impact on the properties of spray-dried dispersions. In this study, the phase behavior of spray-dried dispersions from methanol and methanol-water mixtures was assessed using ritonavir and copovidone [poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA)] as dispersion components.

Novel High-Drug-Loaded Amorphous Dispersion Tablets of Posaconazole; and Assessment.

Amorphous solid dispersions (ASDs) can increase the bioavailability of drugs with poor aqueous solubility. However, concentration-sustaining dispersion polymers (CSPs) incorporated in ASDs can result in low drug loading and, therefore, a large dosage-form size or multiple units to meet dose requirements, potentially decreasing patient compliance. To address this challenge, a high-loaded dosage-form (HLDF) architecture for ASDs was developed, in which a drug is first spray-dried with a high glass-transition temperature () dispersion polymer to facilitate high drug loading while maintaining physical stability.

Solvent-Assisted Secondary Drying of Spray-Dried Polymers.

Purpose: The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spray-drying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spray-drying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas.

A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets.

Although Amorphous Solid Dispersions (ASDs) effectively increase bioavailability, tablet mass can be high due to the large fraction of excipients needed to stabilize the amorphous drug in the solid state, extend drug supersaturation in solution and achieve robust manufacturability. The aim of this work was to reduce tablet mass of an ASD tablet comprising a low glass transition temperature (T), rapidly crystallizing drug without compromising these key attributes. In this approach, erlotinib (T = 42 °C, T/T = 1.

Unlocking the full potential of lipid-based formulations using lipophilic salt/ionic liquid forms.

Lipid-based formulations (LBF) are widely used by industry and accepted by the regulatory authorities for oral drug delivery in the pharmaceutical and consumer healthcare market. Innovation in the LBF field is however needed in order to meet the demands of modern drugs, their more challenging problem statements and growing needs for achieving optimal pharmacokinetics (i.e.

Impact of Drug-Rich Colloids of Itraconazole and HPMCAS on Membrane Flux in Vitro and Oral Bioavailability in Rats.

Improving the oral absorption of compounds with low aqueous solubility is a common challenge that often requires an enabling technology. Frequently, oral absorption can be improved by formulating the compound as an amorphous solid dispersion (ASD). Upon dissolution, an ASD can reach a higher concentration of unbound drug than the crystalline form, and often generates a large number of sub-micrometer, rapidly dissolving drug-rich colloids.

Development of a Biorelevant, Material-Sparing Membrane Flux Test for Rapid Screening of Bioavailability-Enhancing Drug Product Formulations.

Bioavailability-enhancing formulations are often used to overcome challenges of poor gastrointestinal solubility for drug substances developed for oral administration. Conventional in vitro dissolution tests often do not properly compare such formulations due to the many different drug species that may exist in solution. To overcome these limitations, we have designed a practical in vitro membrane flux test, that requires minimal active pharmaceutical ingredient (API) and is capable of rapidly screening many drug product intermediates.