Amorphous solid dispersions enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the link between polymer properties and formulation performance has not been fully clarified yet. We studied the effect of hydroxypropyl cellulose (HPC) polymers molecular weight (M) on the storage stability, dissolution kinetics and supersaturation stability of spray-dried amorphous glibenclamide (GLB) formulations. The solid-state stability of amorphous GLB during storage was significantly enhanced by both the 40 kDa (HPC-SSL) and 84 kDa (HPC-L) polymers, regardless of M differences. In contrast, HPC-SSL maintained significantly higher aqueous drug concentrations during dissolution, compared to HPC-L (its higher M analogue). Dedicated dissolution experiments, in situ optical microscopy and solid-state characterization revealed that aqueous drug concentrations were determined by the interplay between crystallization inhibition, drug ionization, wetting and solubilization effects: (1) HPC prevents surface nucleation, hence inhibiting crystallization, (2) intestinal colloids (bile salts and phospholipids) increase supersaturated drug concentrations via wetting and solubilization effects and (3) pH and drug ionization severely impact the degree of supersaturation. The better performance of the lower M HPC-SSL was due to its superior inhibition of surface crystallization during dissolution. These insights into the molecular mechanisms of dissolution and crystallization of amorphous solids provide foundation for rational formulation development.
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http://dx.doi.org/10.1016/j.ijpharm.2024.124820 | DOI Listing |
Germs
September 2024
MD, PhD, Professor, Department of Orthopedics, Carol Davila University of Medicine and Pharmacy, No. 8 Eroii Sanitari Boulevard, Bucharest, 050474, Romania.
Introduction: This paper examines the use of local antibiotic therapy in one-stage septic revision surgery for late periprosthetic joint infections (PJIs). This case study suggests that morselized bone allografts impregnated with antibiotics in powder form are a preferable alternative to polymethyl methacrylate (PMMA) because they can generate higher local antibiotic concentrations. Current research also recommends using vancomycin and aminoglycosides as the preferred choice of antibiotics, as they may have low diffusion in tissues when administered intravenously, but are effective when administered locally.
View Article and Find Full Text PDFTheranostics
January 2025
Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Radiofrequency ablation (RFA), as a minimally invasive surgery strategy based on local thermal-killing effect, is widely used in the clinical treatment of multiple solid tumors. Nevertheless, RFA cannot achieve the complete elimination of tumor lesions with larger burden or proximity to blood vessels. Incomplete RFA (iRFA) has even been validated to promote residual tumor growth due to the suppressive tumor immune microenvironment (TIME).
View Article and Find Full Text PDFChem Asian J
January 2025
Birla Institute of Technology and Science - Pilani Campus: Birla Institute of Technology & Science Pilani, Pharmacy, BITS Pilani, Pilani campus, Vidya Vihar, 333031, Pilani, INDIA.
In this study, we built on the known inhibitory potential of diaminoquinazolines (DAQs) against different stages of Plasmodium development and designed a convenient two-step synthesis to combine DAQ with the primaquine (PQ) pharmacophore. The PQ-DAQ hybrids displayed potent in vitro activities in the low nanomolar range (IC50 of 135.20-398.
View Article and Find Full Text PDFJ Pharmacokinet Pharmacodyn
January 2025
Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, Leiden, 2333 CC, The Netherlands.
P-glycoprotein (P-gp) is a key efflux transporter and may be involved in drug-drug interactions (DDIs) at the blood-brain barrier (BBB), which could lead to changes in central nervous system (CNS) drug exposure. Morphine is a P-gp substrate and therefore a potential victim drug for P-gp mediated DDIs. It is however unclear if P-gp inhibitors can induce clinically relevant changes in morphine CNS exposure.
View Article and Find Full Text PDFBiomed Chromatogr
February 2025
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Deoxycholic acid (DCA) injection is applied in treating moderate to severe submental bulge or facial fullness caused by excessive submental fat accumulation. Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology, which was swiftly, precisely, and reliably confirmed, DCA was determined in human plasma with low quantification limits of 56 ng/mL. We selected six healthy individual blank human plasma with low concentrations of endogenous DCA and mixed them to prepare standard curve samples.
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