Advancements in techniques of lead molecule selection have resulted in the failure of around 70% of new chemical entities (NCEs). Some of these molecules are getting rejected at final developmental stage resulting in wastage of money and resources. Unfavourable physicochemical properties affect ADME profile of any efficacious and potent molecule, which may ultimately lead to killing of NCE at final stage. Numerous techniques are being explored including nanocrystals for solubility enhancement purposes. Nanocrystals are the most successful and the ones which had a shorter gap between invention and subsequent commercialization of the first marketed product. Several nanocrystal-based products are commercially available and there is a paradigm shift in using approach from simply being solubility enhancement technique to more novel and specific applications. Some other aspects in relation to parenteral nanosuspensions are concentrations of surfactant to be used, scalability and fate. At present, there exists a wide gap due to poor understanding of these critical factors, which we have tried to address in this review. This review will focus on parenteral nanosuspensions, covering varied aspects especially stabilizers used, GRAS (Generally Recognized as Safe) status of stabilizers, scalability challenges, issues of physical and chemical stability, solidification techniques to combat stability problems and fate.
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http://dx.doi.org/10.1016/j.apsb.2018.07.011 | DOI Listing |
Nanomaterials (Basel)
November 2024
College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Chungnam, Republic of Korea.
The aim of the study is to formulate an injectable nanocrystalline suspension (NS) of dutasteride (DTS), a hydrophobic 5α-reductase inhibitor used to treat benign prostatic hyperplasia and scalp hair loss, for parenteral long-acting delivery. A DTS-loaded NS (DTS-NS, 40 mg/mL DTS) was prepared using a lab-scale bead-milling technique. The optimized DTS-NS prepared using Tween 80 (0.
View Article and Find Full Text PDFAAPS PharmSciTech
November 2024
College of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, New York, 11439, USA.
The scarcity of existing and novel therapies for brain cancer has significantly affected the survival rate of glioblastoma patients. Mebendazole (MBZ), an antiparasitic agent demonstrated promising activity against brain cancer. However, poor solubility, multiple polymorphs, and insufficient permeability through blood-brain barrier (BBB) restricts its therapeutic efficacy through parenteral administration.
View Article and Find Full Text PDFJ Pharm Pharmacol
September 2024
Drug Metabolism and Pharmacokinetics, Oncology R&D, AstraZeneca, 35 Gatehouse Park Drive, Waltham, MA 02451, United States.
Objectives: The aim of this study was to investigate the pharmacokinetics (PK) of poorly soluble compounds when administered intramuscularly (i.m.) as crystalline particles of different sizes.
View Article and Find Full Text PDFAnn Pharm Fr
June 2024
Yash institute of pharmacy, Dharmapur, India. Electronic address:
Introduction: Nanosuspensions have emerged as a promising avenue in pharmaceutical innovation, particularly for enhancing the bioavailability of poorly soluble medications. This article explores the transformative potential of nanosuspensions, emphasizing the critical role of particle size reduction through nanonization techniques. With conventional approaches often falling short in addressing the bioavailability challenges of hydrophobic drugs, nanosuspensions offer multifaceted applications and distinctive advantages in drug delivery.
View Article and Find Full Text PDFCurr Pharm Des
November 2023
Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
The poor water solubility of numerous novel drug candidates presents significant challenges, particularly in terms of oral administration. This limitation can result in various undesirable clinical implications, such as inter-patient variability, poor bioavailability, difficulties in achieving a safe therapeutic index, increased costs, and potential risks of toxicity or inefficacy. Biopharmaceutics Classification System (BCS) class II drugs face particular hurdles due to their limited solubility in the aqueous media of the gastrointestinal tract.
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