C. T. Rhodes

Preparation and characterization of liposomes as therapeutic delivery systems: a review

Liposome drug delivery systems are being developed for a variety of drugs. Scale-up process to larger size batches is often a monumental task for the process development scientists. This article reviews various aspects of process development work pertinent to aseptic process techniques for liposomes. This article also has discussed the bilayer properties of liposomes and showed the nomenclature used to classify the liposomes. Discussed is the pH gradient method to load liposomes. Issues and challenges involved in prolonging the shelf-life of liposomes is presented. This review covered the importance of complete removal of organic solvent that is used in the process. Finally the authors presented an HPLC method for quick identification and assay of various phospholipids in a mixture of phospholipids.

Development of a Novel Controlled-Release System for Gastric Retention

AbstractPurpose. We report on the development of a novel controlled-release gastric retention system, which consists of a matrix tablet, coated with a permeable membrane. When immersed in simulated gastric fluid, the tablet expands. The tablet remains expanded for eighteen to twenty hours, during which time the drug is released. The tablet then either disintegrates into fragments or loses its integrity. Methods. Tablets containing a soluble drug (chlorpheniramine maleate, i.e., CPM) and a poorly soluble drug (riboflavin 5′ phosphate, i.e., R5′P) were compressed. They were coated with a permeable and elastic polymer (Eudragit®). Dissolution profiles of these tablets were studied. The changes in the pH, viscosity, and deformation characteristics as a function of time were measured. Results. Carbopol® provided a firm structure to the swollen tablet. Polyvinyl pyrrolidone XL (PVP XL) contributed to the swelling of the tablet. Carbonates provided the initial alkaline micro-environment for Carbopol® to gel and conferred buoyancy to the tablet. Coating provided the support needed for the core to remain intact during drug release and, at the same time, it allowed drug release due to its permeable nature. During release, the gelling properties of Carbopol® lessened, resulting in a decrease in the firmness of the core. This was evident from the decrease in the viscosity of the core. The energy required at 50% strain also decreased as the drug release progressed. Conclusions. When this tablet is ingested, the chances of its elimination through the pylorus should be greatly reduced due to tablets expansion, and due to its disintegration or loss in integrity it should then be expelled out of the stomach at the end of the drug release.

Controlled-Release Drug Delivery Systems for Prolonged Gastric Residence: An Overview

(1996). Controlled-Release Drug Delivery Systems for Prolonged Gastric Residence: An Overview. Drug Development and Industrial Pharmacy: Vol. 22, No. 6, pp. 531-539.

Controlled Drug Delivery by Biodegradable Poly(Ester) Devices: Different Preparative Approaches

There has been extensive research on drug delivery by biodegradable polymeric devices since bioresorbable surgical sutures entered the market two decades ago. Among the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) such as poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide referred to as poly(lactide-co-glycolide) (PLGA) have generated tremendous interest because of their excellent biocompatibility, biodegradability, and mechanical strength. They are easy to formulate into various devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Most importantly, they have been approved by the United States Food and Drug Administration (FDA) for drug delivery. This review presents different preparation techniques of various drug-loaded PLGA devices, with special emphasis on preparing microparticles. Certain issues about other related biodegradable polyesters are discussed.

Design and testing in vitro of a bioadhesive and floating drug delivery system for oral application

Abstract A new drug delivery system for a water-soluble beta-blocker drug, sotalol HCl, was developed utilizing both the concepts of adhesiveness and of flotation, in order to obtain a unique drug delivery system which could remain in the stomach for a much longer period of time. The floating and controlled-release properties of tablets consisting of cellulosic polymers were investigated. In order to validate the technological design of the new system, two different batches were made. In both cases, the time necessary for the tablets to begin to float was less than 30 min. Moreover, 90% of the drug content was released during the first 14 h. The bioadhesive property of the tablets was determined using rabbit tissue and a modified tensiometer. The new oral controlled-release system shows, at least in vitro, good characetristics in relation to three parameters: controlled release of the drug, bioadhesiveness in the stomach and intestine of rabbits and buoyancy in an acid medium.

Mucoadhesive Drug Delivery Systems

AbstractPharmaceutical aspects of mucoadhesion have been the subject of great interest during recent years because mucoadhesion could be a solution for bioavailability problems that result from a too short length of stay of the pharmaceutical dosage form at the absorption site within the gastro-intestinal tract.This paper describes some aspects of bioadhesion such as mucus structure, stages of adhesion and the theories proposed that attempt to explain the adhesion mechanism. The factors that affect the bioadhesive power of a polymer, the methods that permit the evaluation of a bioadhesive system and the methods for surface characterization of biomaterials are discussed. Finally, the various polymers used and the bioadhesive systems designed for several therapeutic purposes are presented.

Optimization of Sotalol Floating and Bioadhesive Extended Release Tablet Formulations

AbstractA novel extended release sotalol HC1 tablet formulation which possesses a unique combination of floatation and bioadhesion for prolonged residence in the stomach has been developed. Tablets were produced by direct compression. A two-factor factorial, central, composite Box-Wilson experimental design was employed to develop and optimize the tablet formulation containing 240 mg sotalol HC1. The ratio of two major bioadhesive agents, sodium carboxymethylcellulose (NaCMC) to hydroxypropylmethylcellulose (HPMC), and the ratio of two direct compressible diluents, ethylcellulose (EC) to crosspovidone, were used as formulation variables (independent variables) for optimizing tablets response parameters, such as dissolution bioadhesive capability, tablet density and required compression force for producing 6 Kg hardness tablets. The data were also analyzed by means of quadratic response surface model. Response surfaces were generated as a function of formulation variables. An optimum direct compression, bi...

Trends in stability testing, with emphasis on stability during distribution and storage

This paper reviews contemporary trends in the stability testing of pharmaceutical products. In particular, it considers the progress toward globalization and harmonization and indicates stability problems, which probably will be the focus of attention for pharmaceutical scientists and regulators in the near future. Attention is specifically directed to monitoring stability in the channels of distribution.

Near-Infrared Spectroscopy as a Nondestructive Alternative to Conventional Tablet Hardness Testing

AbstractPurpose. Near-infrared reflectance Spectroscopy (NIRS) was used to evaluate and quantify the effect of compression force on the NIR spectra of tablets. Methods. Flat, white tablets with no orientation (scoring, etc.) were manufactured on a Stokes Rotary Tablet Press. NIRS was used to predict tablet hardness on the following four formulations and one placebo matrix: hydrochlorothiazide (HCTZ) 15% and 20% in a placebo matrix (microcrystalline cellulose and magnesium stearate), and chlorpheniramine maleate (CTM) 2% and 6% in a placebo matrix. Five or six levels of tablet hardness from 2 to 12 kg were used for each formulation. Laboratory hardness data was compared to NIR reflectance data using a NIRSystems Rapid Content Analyzer®. Multiple linear regression and partial least squares regression techniques were used to determine the relationship between tablet hardness and NIRS spectra. Results. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIRS spectra. A series of equations was developed by calibrating tablet hardness data against NIR reflectance response for each formulation. The results of NIRS hardness prediction were at least as precise as the laboratory hardness test (SE = 0.32). Conclusions. A NIRS method is presented which has the potential as an alternative to conventional hardness testing of tablets.

The development of USP dissolution and drug release standards

Dissolution tests have been in use in the pharmaceutical industry for over 20 years, and they are official in The United States Pharmacopeia since the early 1960s. The dissolution test, reviewed primarily as a quality control tool, replaced the use of disintegration tests which had been official in The United States Pharmacopeia since 1950. Refinements in the dissolution test equipment and methodology have occurred over the years in order to enhance its relevance. The Subcommittees of the USP Committee of Revision dealing with these issues have developed and refined compendial dissolution standards and policies for conventional solid-oral dosage forms and modified-release dosage forms.