Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
21
3
2004
Amorphous Drug Delivery Systems: Molecular Aspects, Design, and Performance
62
10.1615/CritRevTherDrugCarrierSyst.v21.i3.10
Aditya Mohan
Kaushal
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India
Piyush
Gupta
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India
Arvind Kumar
Bansal
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India
The biopharmaceutical properties—especially the solubility and permeability—of a molecule contribute to its overall therapeutic efficacy. The newer tools of drug discovery have caused a shift in the properties of drug-like compounds, resulting in drugs with poor aqueous solubility and permeability, which offer delivery challenges, thus requiring considerable pharmaceutical manning. The modulation of solubility is a more viable option for enhancing bioavailability than permeability, because of the lack of "safe" approaches to enhance the latter. Solid-state manipulation in general, and amorphization in particular, are preferred ways of enhancing solubility and optimizing delivery of poorly soluble drugs. This review attempts to address the diverse issues pertaining to amorphous drug delivery systems. We discuss the various thermodynamic phenomenon such as glass transition, fragility, molecular mobility, devitrification kinetics, and molecular-level chemical interactions that contribute to the ease of formation, the solubility advantage, and the stability of amorphous drugs. The engineering of pharmaceutical alloys by solubilizing and stabilizing carriers, commonly termed solid dispersions, provide avenues for exploiting the benefits of amorphous systems. Carrier properties, mechanisms of drug release, and study of release kinetics help to improve the predictability of performance. The review also addresses the various barriers in the design of amorphous delivery systems, use of amorphous form in controlled release delivery systems, and their in vivo performance.
Mucosal Drug Delivery: Membranes, Methodologies, and Applications
62
10.1615/CritRevTherDrugCarrierSyst.v21.i3.20
Yifan
Song
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, Lab for Drug Delivery, Newark, New Jersey, USA
Yiping
Wang
Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA
Rashmi
Thakur
Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA
Victor M.
Meidan
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, Scotland UK
Bozena
Michniak
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, Lab for Drug Delivery, Newark, New Jersey; University of South Carolina, Basic Pharmaceutical Sciences, 700 Sumter St., Columbia, SC 29208, USA
In recent years, extensive research into novel forms of drug delivery has suggested that mucosal approaches offer a promising therapeutic alternative, especially for systemically acting drugs. Transmucosal drug delivery offers many benefits, including noninvasive administration, convenience, rapid onset, as well as elimination of hepatic first-pass metabolism. The investigated absorptive surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among these, the nasal and buccal routes have proved the most promising to date. The bioavailability achieved mainly depends upon the pathophysiological state of the mucosa and the properties of both the drug and delivery systems. Various agents can increase the efficacy of transmucosal drug delivery. These include cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres, liposomes, and bioadhesive agents.The mechanisms of action, effectiveness, and toxicity profiles of these enhancers have been investigated extensively in both animal and human models.