In vitro release of metoclopramide from hydrophobic matrix tablets. influence of hydrodynamic conditions on kinetic release parameters.
There has been growing interest in the subject of drug delivery and the design and evaluation of controlled-release systems. The simplest way to control the release of an active agent is to disperse it in an inert polymeric matrix. Controlled-release systems are of interest because they are technologically simple, relatively cheap, and practically unaffected by physiological changes. In this study, a new matrix system was formed by an active principle, metoclopramide hydrochloride, scattered into a biocompatible hydrophobic polymerical mesh, polyamide 12, to achieve sustained and controlled delivery of metoclopramide hydrochloride. This research was conducted to investigate the in vitro drug release behavior from these new inert polymeric matrix tablets. The drug release process was investigated both experimentally and by means of mathematical models. Different models were applied for the evaluation of drug release data. On the basis of our results, a biexponential equation was proposed, Q=Qfast(1)(1 - e(-Kfast t)) + Qslow(2)(1 - e(-Kslow t)), in an attempt to explain the mechanism responsible for the release process. Additionally, the influence of the experimental conditions of the dissolution devices, such as rate of flow and pH of dissolution medium, on the parameters that characterize the release mechanism was studied, and it was found that the main factor was the hydrodynamic condition of rate of flow.
Microstructural Analysis of Porous Composite Materials: Dynamic Imaging of Drug Dissolution and Diffusion Through Porous Matrices
The dissolution and diffusion of molecules through porous materials is of great interest to many researchers and can be found in diverse areas of science including catalyst manufacture, food and cosmetic production, tissue engineering, and a whole range of medicines. In terms of conventional medicines, tablets are by far the most popular formulations on the market and are preferred by patients and physicians alike. However, the science underpinning the design and function of more complex formulations, specifically those with controlled release profiles, is lacking in some respect. Due to their ease of manufacture and low costs, the simplest form of controlled release tablet is the matrix tablet (1–3). Matrix-based systems are usually obtained by direct compression of an active (drug) blended with retardant material and additives to form a simple matrix (3,4), in which the nature of the retardant material, which is usually a polymer, determines the nature of the matrix formed. If hydrophobic materials such as wax and ethyl cellulose are used, they form porous matrices, which may be either inert or erodable (1,3). In theory, the retardant material in the inert matrix controls drug release by forming an inert diffusion barrier around the drug particles (4). Clearly, the liquid media must penetrate the matrix to allow the drug to be released from the matrix via diffusion and finally dissolution (3); thus, porosity is a key parameter (5,6). Production and manufacture variables encountered during the production of matrix-based materials lead to variations in performance and therefore jeopardise regulatory acceptance. 
 
Subsequently, it would be advantageous to visualise the internal structure of such materials post-manufacture and focus on the dynamic property of pore structure and porosity during dissolution and diffusion. X-ray microtomography (XCMT) can produce 3D images of materials with a voxel size of around several micrometers cubed, allowing the visualisation of internal and microstructural details with different X-ray absorbencies. The intensity values associated with the different features of an XCMT image are determined by the X-ray transmission measured by an X-ray detection system, which is dependent on the material’s atomic mass and the energy of X-rays (7,8). 
 
In a previous study, the investigators have focused on the use of XCMT for the study of modified release systems (Adalat® OROS, Alza Corporations OROS® technology, Alza, CA, USA). These formulations contain different excipients (swellable polyethylene oxide polymer), sodium chloride crystals, and nifedipine (active drug). All components were easily resolved by XCMT due to their inherent variations in density, giving evidence of the scope of applicability of the method (9). 
 
For this specific investigation, the goal was to evaluate XCMT as a nondestructive imaging technique, to study porous matrix structure and the diffusion and dissolution process that occurs during drug release. Inert matrix tablets (Ferrogradumet®, Abbott Laboratories, Australia) containing ferrous sulphate in a matrix of lactose and Eudragit® were chosen as the model tablets and evaluated using the XCMT at set time points during dissolution using a custom-built sample mount.
Continuous Intrathecal Infusion of Opioid and Bupivacaine in the Treatment of Refractory Pain Due to Postherpetic Neuralgia: A Case Report
This report details the course of a 77‐year‐old patient suffering mild pain from operated tongue cancer and excruciating, intractable pain from thoracic (T6–T8) post‐herpetic neuralgia (PHN), The mouth pain was treated with nonopioid analgesics, as the patient had personal objections to opioid treatment. All the components of the pain from his PHN (continuous burning pain, intermittent lancinating stabbing pain, and tactile allodynia) were successfully treated with an Intrathecal Infusion of buprenorphine (0.03 mg/ml) and bupivacaine (4.75 mg/ml) administered via an externalized intrathecal catheter with the tip located at T9–T10 intervertebral disc. The treatment started three months after the appearance of the herpetic eruption and lasted 294 days until the patient died of malnutrition and the progression of his tongue cancer. During treatment, he experienced satisfactory pain relief from his PHN; the mean visual analogue scores (VASmean), recorded on a scale from 0 to 10, ranged from 1 to 2, compared to 9 to 10 before starting the intrathecal treatment. Analgesia was established with 0.2–0.315 mg/day of intrathecal buprenorphine and 90–100 mg/day of intrathecal bupivacaine. His undisturbed nocturnal sleep increased from 4 to 5–6 hours. The side‐effects from the bupivacaine (urine retention requiring insertion of an indwelling urinary catheter, paresthesias, and mild pareses) were recorded. The patient could ambulate without support while on 90–100 mg/day of intrathecal bupivacaine. During a series of high‐pressure oxygen treatments in a pressure chamber to treat an infection at the site of his tumor, the intrathecal infusion was interrupted. Thus, repeated observation of the intervals of severe pain and of analgesia were possible.