A novel pH-dependant and double crosslinked polymethacrylate-based polysphere matrix for enteric delivery of isoniazid.

This study aimed at developing double crosslinked isoniazid (INH)-loaded polymethyl-methacrylate-ethylcellulose (PMMA-EC) polyspheres for rate-controlled enteric drug delivery. A PMMA solution was manipulated with the addition of EC to produce polyspheres by drop-wise extrusion into a primary crosslinking solution of AlCl3 (25% w/v), before adding a second crosslinking solution of either 30% w/v BaCl2 (polysphere Batch A) or 30% w/v MgCl2 (polysphere Batch B). The polyspheres were then subjected to FTIR spectroscopic analysis, in vitro drug release studies, drug entrapment efficiency (DEE) determination as well as surface area and porositometric investigations. Molecular Mechanics (MM) simulations elucidated the interaction between the cations and the PMMA-EC combination. FTIR spectra revealed an affinity of PMMA for Ba(2+), Mg(2+) and Al(3+). SEM showed smooth robust polyspheres ranging between 4-6 mm. Porositometric analysis established that polysphere Batch A had larger pores (315.314 Åabs) than Batch B (234.603 Åabs). Drug release profiles from polysphere Batch A displayed burst release with 50% INH released within 2 h (N = 3) that was attributable to the larger ionic radius of the second crosslinker Ba(2+) compared Mg(2+) which was employed for polysphere Batch B. The latter produced polyspheres with superior control in INH release (<25% within 2 h) (N = 3) and a higher DEE with minimal pore formation. The experimental findings were well corroborated by the MM simulations.

Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery.

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix(®) multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise(®), which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix(®) as well as "release modules assemblage", which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

A review of multi-responsive membranous systems for rate-modulated drug delivery.

Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is a behavior that can be utilized to prepare 'smart' drug delivery systems. Stimuli-responsive or 'smart' polymers are polymers that upon exposure to small changes in the environment undergo rapid changes in their microstructure. A stimulus, such as a change in pH or temperature, thus serves as a trigger for the release of drug from membranous drug delivery systems that are formulated from stimuli-responsive polymers. This article has sought to review the use of stimuli-responsive polymers that have found application in membranous drug delivery systems. Polymers responsive to pH and temperature have been extensively addressed in this review since they are considered the most important stimuli that may be exploited for use in drug delivery, and biomedical applications such as in tissue engineering. In addition, dual-responsive and glucose-responsive membranes have been also addressed as membranes responsive to diverse stimuli.