Impact of HPMCAS Grade on the Release of Weakly Basic Drugs from Amorphous Solid Dispersions.

Oppositely charged species can form electrostatic interactions in aqueous solution, and these may lead to reduced solubility of the interacting components. Herein, insoluble complex formation between the lipophilic weakly basic drugs, cinnarizine or loratadine, and the enteric polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), was studied and used to better understand drug and polymer release from their corresponding amorphous solid dispersions (ASDs). Surface area normalized release experiments were performed at various pH conditions for three different grades of HPMCAS, LF, MF and HF, as well as their ASDs.

Culturally Tailored Messages and Trial Registry Enrollment: A Randomized Clinical Trial.

Importance: Marginalized populations have lower levels of clinical trial representation than other populations. Tailoring recruitment materials and providing incentives may improve representation.

Objective: To determine whether culturally tailored video improves parents' decision to enroll (DTE) Black children in a research registry.

ω-Carboxyl terminated cellulose esters are effective crystallization inhibitors for challenging drugs.

Polymeric additives are widely used to delay drug crystallization from supersaturated solutions, which is critical for enhancing oral bioavailability by amorphous solid dispersion (ASD). The efficacy of these polymers relies on their capacity to inhibit nucleation and subsequent crystal growth. Drug nucleation is pivotal to crystallization; therefore, effective polymers are essential for suppressing nucleation from supersaturated solutions.

Dissolution mechanisms of amorphous solid dispersions: Role of polymer molecular weight and identification of a new failure mode.

The mechanisms of drug release from amorphous solid dispersions (ASDs) are complex and not fully explored, making it difficult to optimize for in vivo performance. A recurring behavior has been the limit of congruency (LoC), a drug loading above which the ASD surface forms an amorphous drug-rich barrier in the presence of water, which hinders release, especially in non-sink conditions. Drug-polymer interactions and drug glass transition temperature were reported to affect the LoC.

Impact of drug incorporation into micelle on reduced griseofulvin and meloxicam permeation across a hollow fiber membrane.

A hollow fiber membrane (HFM) was previously characterized as a potential permeation component of a dissolution/permeation system. Two objectives were to assess the impact of micellization on drug permeation across HFM and identify a preferred permeation model from three models: permeation from only free drug, permeation from both free drug and micelle-bound drug, and permeation with enhancement from micelle shuttling. HFM studies were conducted under unsaturated drug conditions, using griseofulvin and the more hydrophilic drug meloxicam, with and without surfactant [sodium lauryl sulfate, polysorbate 80, and polyoxyethylene (10) lauryl ether].

Dissolution, phase behavior and mass transport of amorphous solid dispersions in aspirated human intestinal fluids.

Amorphous solid dispersions (ASDs) typically show improved dissolution and generate supersaturated solutions, enhancing the oral bioavailability of poorly soluble drugs. To gain insights into intraluminal ASD behavior, we utilized two poorly soluble drugs with different crystallization tendencies, atazanavir and posaconazole, prepared as ASDs at a 10% drug loading with hydroxypropyl methylcellulose acetyl succinate (HPMCAS). We evaluated their release in aspirated fasted-state human intestinal fluid (FaHIF), and multi-component fasted-state simulated intestinal fluid (composite-FaSSIF), characterizing the supersaturation profiles and drug-rich nanodroplets that formed.

Amorphous Solid Dispersion Formation for Enhanced Release Performance of Racemic and Enantiopure Praziquantel.

Praziquantel (PZQ) is the treatment of choice for schistosomiasis, which affects more than 250 million people globally. Commercial tablets contain the crystalline racemic compound (-PZQ) which limits drug dissolution and oral bioavailability and can lead to unwanted side effects and poor patient compliance due to the presence of the -enantiomer. While many approaches have been explored for improving PZQ's dissolution and oral bioavailability, studies focusing on investigating its release from amorphous solid dispersions (ASDs) have been limited.

Identifying research priorities and essential elements of palliative care services for people facing malignant brain tumors: A participatory co-design approach.

Background: Primary malignant brain tumors (ie, brain cancer) impact the quality of life (QoL) for patients and care partners in disease-specific ways involving cognition and communication. Palliative care (PC) addresses patient/care partner QoL, but it is not known how PC may address the unique needs of brain cancer patients. The purpose of this project was to identify brain cancer PC research priorities using participatory co-design methods.

Chemistry and ionization of HPMCAS influences the dissolution and solution-mediated crystallization of posaconazole amorphous solid dispersions.

Hydroxypropyl methyl cellulose acetate succinate (HPMCAS) is one of the polymers of choice in formulating amorphous solid dispersions (ASDs) and helps to sustain high levels of drug supersaturation by delaying drug crystallization. Herein, the impact of HPMCAS chemistry on the solution crystallization kinetics of a fast-crystallizing lipophilic drug, posaconazole (PCZ), from the aqueous bulk phase and the drug-rich phase generated by liquid-liquid phase separation (LLPS), was studied. Three grades of HPMCAS: L, M, and H, which differ in the degree of acetyl and succinoyl substitution (A/S ratio), were compared.

Amorphous solubility advantage: Theoretical considerations, experimental methods, and contemporary relevance.

Twenty-five years ago, Hancock and Parks asked a provocative question: "what is the true solubility advantage for amorphous pharmaceuticals?" Difficulties in determining the amorphous solubility have since been overcome due to significant advances in theoretical understanding and experimental methods. The amorphous solubility is now understood to be the concentration after the drug undergoes liquid-liquid or liquid-glass phase separation, forming a water-saturated drug-rich phase in metastable equilibrium with an aqueous phase containing molecularly dissolved drug. While crystalline solubility is an essential parameter impacting the absorption of crystalline drug formulations, amorphous solubility is a vital factor for considering absorption from supersaturating formulations.

Exploring biorelevant conditions and release profiles of ritonavir from HPMCAS-based amorphous solid dispersions.

Development of a release test for amorphous solid dispersions (ASDs) that is in vivo predictive is essential to identify optimally performing formulations early in development. For ASDs containing an enteric polymer, consideration of buffer properties is essential. Herein, release rates of hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and ritonavir from ASDs with a 20% drug loading were compared in phosphate and bicarbonate buffers with different molarities, at pH 6.

6-Carboxycellulose Acetate Butyrate: Effectiveness as an Amorphous Solid Dispersion Polymer.

Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature () polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential.

Diffusion Mapping with Diffractive Optical Elements for Periodically Patterned Photobleaching.

Fourier transform-fluorescence recovery after photobleaching (FT-FRAP) using a diffractive optical element (DOE) is shown to support distance-dependent diffusion analysis in biologically relevant media. Integration of DOEs enables patterning of a dot array for parallel acquisition of point-bleach FRAP measurements at multiple locations across the field of view. In homogeneous media, the spatial harmonics of the dot array analyzed in the spatial Fourier transform domain yield diffusion recovery curves evaluated over specific well-defined distances.

Characterizing Walking Behaviors in Aged Residential Care Using Accelerometry, With Comparison Across Care Levels, Cognitive Status, and Physical Function: Cross-Sectional Study.

Background: Walking is important for maintaining physical and mental well-being in aged residential care (ARC). Walking behaviors are not well characterized in ARC due to inconsistencies in assessment methods and metrics as well as limited research regarding the impact of care environment, cognition, or physical function on these behaviors. It is recommended that walking behaviors in ARC are assessed using validated digital methods that can capture low volumes of walking activity.

Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.

Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior.

The use of amorphous solid dispersions (ASDs) in commercial drug products has increased in recent years due to the large number of poorly soluble drugs in the pharmaceutical pipeline. However, the release behavior of ASDs is complex and remains not well understood. Often, the drug release from ASDs is rapid and complete at lower drug loadings (DLs) but becomes slow and incomplete at higher DLs.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

Purpose: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors.

Interplay of Drug-Polymer Interactions and Release Performance for HPMCAS-Based Amorphous Solid Dispersions.

The interplay between drug and polymer chemistry and its impact on drug release from an amorphous solid dispersion (ASD) is a relatively underexplored area. Herein, the release rates of several drugs of diverse chemistry from hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based ASDs were explored using surface area normalized dissolution. The tendency of the drug to form an insoluble complex with HPMCAS was determined through coprecipitation experiments.