Use of crospovidone as pelletization aid as alternative to microcrystalline cellulose: effects on pellet properties.

BACKGROUND: Microcrystalline cellulose (MCC) is the most important pelletization aid in extrusion/spheronization. Because of known disadvantages, the search for substitutes is ongoing. In this context, crospovidone has proven to offer substantial advantages as pelletization aid because of its ability to turn low-soluble active ingredients into fast-dissolving stable pellets. METHOD: Pellets from crospovidone with different amounts of paracetamol, hydrochlorothiazide, and spironolactone as model drugs were prepared by extrusion/spheronization. For comparison, pellets with MCC as extrusion aid were also produced. The pellets of different formulations were evaluated in terms of yield, aspect ratio, mean Feret diameter, 10% interval fraction, tensile strength, disintegration, and drug release profile. RESULTS: Only crospovidone types exhibiting small particle sizes are suitable as pelletization aid. While maintaining the pharmaceutical quality aspects, it was possible to incorporate up to 60% (w/w) active pharmaceutical ingredients (API) into pellets with crospovidone. The most distinguished differences between pellets based on crospovidone and MCC are the disintegration and drug release behavior. The pellets containing binary mixtures of the low-soluble APIs and crospovidone resulted in fast release in contrast to the pellets with MCC as pelletization aid, which exhibited a slow release. CONCLUSION: Crospovidone shows an excellent behavior as pelletization aid and produces fast-releasing pellets even with low-soluble APIs.

[Reintervention after endoscopic surgery of the carpal tunnel syndrome]. / Nachoperationen nach endoskopisch voroperiertem Karpaltunnelsyndrom.

BACKGROUND: The carpal tunnel syndrome is one of the most frequent peripheric nerve compression syndromes. Almost 15 years ago, the endoscopic surgery of the carpal tunnel was introduced, in order to reduce postoperative pain and to shorten the length of the postoperative inactivity period, especially work absence. In the literature the rate of complications due to the endoscopic carpal tunnel release surgery is reported differently in respect to number and severity. This paper summarizes all reinterventions after endoscopic surgery in a single specialized hand surgery department, which prefers the open approach even for first time interventions. PATIENTS AND METHOD: A retrospective analysis of all reoperations between 1998 and 2006 is presented. There were 22 reinterventions done on 21 patients. A reoperation was performed if the symptoms of the carpal tunnel syndrome persisted or new pain or sensomotor deficit appeared. There were 8 male and 14 female patients. The age span ranged from 28 to 86 years. The time distance between the first and the second surgery was between 19 days and 36 months. RESULTS: Most of the intraoperative findings were incomplete releases of the retinaculum (n = 13). In three cases abundant adherences caused the clinical symptoms. Three times pathologies were found in carpal tunnel, which could not be recognized or treated endoscopically: severe bleeding in the synovia, massive synovialitis and a swannoma of the median nerve. In seven patients transsected nerves had to be treated: one complete transsection of the median nerve, two nerves with injured radial fascicles, two nerves with violated ulnar fascicles, one neuroma of the median nerve and one transsection of both branches of the ulnar nerve. CONCLUSION: In 22 cases the result of the endoscopic release of the carpal tunnel forced to redo the intervention. In seven patients there were important lesions of the neurovascular structures. Since the long-term result of the endoscopic and open surgery of the carpal tunnel is comparable, it should be discussed if endoscopic surgery is justified even with the risk of mutilant complications and which preoperative imaging procedure is required to discover pathologies and anatomical variants.

Press chamber coating as external lubrication for high speed rotary presses: lubricant spray rate optimization.

Lubrication of the tooling (punches and dies) is necessary to produce tablets. The most commonly used lubricant is magnesium stearate. Adding and blending magnesium stearate to the tablet mass often has negative effects on the properties of the compressed tablets (e.g., decreasing the tensile strength of the tablet). To avoid these negative effects, external lubrication systems were developed. This study investigated the functionality and the influence of a new press chamber coating system called the PKB II. The major difference between the PKB II and previous systems is its ability to spray a mixture of powdered magnesium stearate and air directly onto the punches and dies which was determined to allow the running of the rotor at higher speeds. The data showed a clear correlation between the spray rate of the lubricant and the concentration of the magnesium stearate per tablet. The PKB II was designed to allow for adjustments, in order to optimize the spray rate, by using the ejection force. The concentration of magnesium stearate was reduced to approximately 0.04% per tablet, using the PKB II. Additionally, the most common negative effects, such as the decrease in tablet tensile strength, were avoided by using this system.

Quantifying low amorphous or crystalline amounts of alpha-lactose-monohydrate using X-ray powder diffraction, near-infrared spectroscopy, and differential scanning calorimetry.

Efficient and accurate quantification of low amorphous and crystalline contents within pharmaceutical materials still remains a challenging task in the pharmaceutical industry. Since X-ray powder diffraction (XRPD) equipment has improved in recent years, our aim was 1) to investigate the possibility of substantially lowering the detection limits of amorphous or crystalline material to about 1% or 0.5% w/w respectively by applying conventional Bragg Brentano optics, combined with a fast and simple evaluation technique; 2) to perform these measurements within a short time to make it suitable for routine analysis; and 3) to subject the same data sets to a partial least squares regression (PLSR) in order to investigate whether it is possible to improve accuracy and precision compared to the standard integration method. Near-infrared spectroscopy (NIRS) and differential scanning calorimetry (DSC) were chosen as reference method. As model substance, alpha lactose monohydrate was chosen to create calibration curves based on predetermined mixtures of highly crystalline and amorphous substance. In contrast to DSC, XRPD and NIRS revealed an excellent linearity, precision, and accuracy with the percent of crystalline amount and a detectability down to about 0.5% w/w. Chemometric evaluation (partial least squares regression) applied to the XRPD data further improved the quality of our calibration.

Intermittent axillary nerve palsy caused by a humeral exostosis.

We report an uncommon case of intermittent axillary nerve palsy caused by a humeral exostosis in an 11-year-old boy. After excision of the cartilagenous exostosis of the proximal end of the left humerus, the pre-operative symptoms of axillary nerve compression were alleviated.