Abstract
A large number of the new pharmaceutical small molecules under development today are found to have poor water solubility. This in turn may lead to low bioavailability, which can have a significant impact on the development of the compound. Compounds with low bioavailability pose a greater challenge in early preclinical work involving animal studies, where obtaining maximum exposure is the primary goal especially in toxicology studies designed to establish the safe dose. From the standpoint of maximizing exposure, the amorphous phase is of great interest as pharmaceutical materials since it is the most metastable state and as such offers the potential of higher solubility and better bioavailability. However, the amorphous approach is not actively pursued in preclinical work owing to the tendency of the amorphous phase to crystallize thereby neutralizing the solubility advantage. This review focuses on (i) methods to generate the amorphous phase, (ii) methods to estimate the degree of crystallinity of the amorphous phase, (iii) methods to predict the stability of the amorphous phase against crystallization, and (iv) choice of polymers carrier and formulation of the amorphous phase for preclinical studies.
Keywords: Amorphous pharmaceuticals, crystallization, preclinical, solid dispersions
Current Bioactive Compounds
Title: Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation
Volume: 4 Issue: 4
Author(s): Karthik Nagapudi and Janan Jona
Affiliation:
Keywords: Amorphous pharmaceuticals, crystallization, preclinical, solid dispersions
Abstract: A large number of the new pharmaceutical small molecules under development today are found to have poor water solubility. This in turn may lead to low bioavailability, which can have a significant impact on the development of the compound. Compounds with low bioavailability pose a greater challenge in early preclinical work involving animal studies, where obtaining maximum exposure is the primary goal especially in toxicology studies designed to establish the safe dose. From the standpoint of maximizing exposure, the amorphous phase is of great interest as pharmaceutical materials since it is the most metastable state and as such offers the potential of higher solubility and better bioavailability. However, the amorphous approach is not actively pursued in preclinical work owing to the tendency of the amorphous phase to crystallize thereby neutralizing the solubility advantage. This review focuses on (i) methods to generate the amorphous phase, (ii) methods to estimate the degree of crystallinity of the amorphous phase, (iii) methods to predict the stability of the amorphous phase against crystallization, and (iv) choice of polymers carrier and formulation of the amorphous phase for preclinical studies.
Export Options
About this article
Cite this article as:
Nagapudi Karthik and Jona Janan, Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation, Current Bioactive Compounds 2008; 4 (4) . https://dx.doi.org/10.2174/157340708786847852
DOI https://dx.doi.org/10.2174/157340708786847852 |
Print ISSN 1573-4072 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6646 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Therapeutic Modulation of Growth Factors and Cytokines in Regenerative Medicine
Current Pharmaceutical Design Indoleamine 2,3-Dioxygenase in Immune Suppression and Cancer
Current Cancer Drug Targets The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic Stimulation) in Depression: A Mini-Review in Animal Studies
Medicinal Chemistry Identifying Alzheimer’s Disease-related miRNA Based on Semi-clustering
Current Gene Therapy Postoperative COVID-19 Pneumonia in an Asymptomatic Patient: A Case Report
Infectious Disorders - Drug Targets Enriched Environments for Rodents and their Interaction with Nicotine Administration
Current Drug Abuse Reviews Anti-Inflammatory Therapy for Alzheimer’s Disease from Epidemiological Fact to New Mechanisms of Action
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Bile Acids and Derivatives, Their Nuclear Receptors FXR, PXR and Ligands: Role in Health and Disease and Their Therapeutic Potential
Anti-Cancer Agents in Medicinal Chemistry Neurobiology of Bipolar Disorder: Abnormalities on Cognitive and Cortical Functioning and Biomarker Levels
CNS & Neurological Disorders - Drug Targets Mitochondrial Biogenesis: Regulation By Endogenous Gases During Inflammation and Organ Stress
Current Pharmaceutical Design LPS-induced Murine Neuroinflammation Model: Main Features and Suitability for Pre-clinical Assessment of Nutraceuticals
Current Neuropharmacology Active Targeting Towards and Inside the Brain based on Nanoparticles: A Review
Current Pharmaceutical Biotechnology Management Of Elderly Patients With Diffuse Large B-Cell Lymphomas
Anti-Cancer Agents in Medicinal Chemistry Von Willebrand Factor: Drug and Drug Target
Cardiovascular & Hematological Disorders-Drug Targets Biological Markers for Multiple Sclerosis
Current Medicinal Chemistry Ampelopsin Improves Cognitive Impairment in Alzheimer’s Disease and Effects of Inflammatory Cytokines and Oxidative Stress in the Hippocampus
Current Alzheimer Research Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives
Current Neuropharmacology Older Adults Prescribed Methadone: A Review of the Literature Across the Life Span from Opiate Initiation to Methadone Maintenance Treatment
Current Drug Abuse Reviews Methylene Blue and Vasoplegia: Who, When, and How?
Mini-Reviews in Medicinal Chemistry The Role of Atypical Antipsychotics in Sexuality: Road to Recovery in Schizophrenia
Current Drug Targets