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.

[Misinterpretation of a solitary breast carcinoma metastasis of the hand as an enchondroma. Case report and literature review]. / Fehlinterpretation einer solitären Mammakarzinommetastase in der Hand als Enchondrom. Fallbericht und Literaturübersicht.

Carcinoma of the breast is the third most common primary tumor leading to metastases in the hand. It is preceded by carcinoma of the lung and kidney. A review of literature is presented, following the case report of an isolated skeletal metastasis in the middle phalanx of the left ring finger in a 67-year-old patient seven years after mastectomy of the right breast. At first, the findings were misinterpreted as enchondroma.

C-terminal domains of general regulatory factors Abf1p and Rap1p in Saccharomyces cerevisiae display functional similarity.

Abf1p and Rap1p are global regulatory factors which play an essential role in the transcription activation of yeast ribosomal protein genes. This functional link prompted us to investigate whether these factors may be functionally interchangeable. We focused on the indispensable C-terminal portions of both factors and performed mutual domain swaps. The functional capacity of the resulting hybrid proteins was subsequently examined using yeast strains conditionally expressing either the ABF1 or the RAP1 gene. Both the Abf1p-Rap1p and the Rap1p-Abf1p fusion proteins were found to be able to complement the growth defect of the respective strains. Furthermore, Abf1p and Rap1p are both able to promote transcription of a reporter gene through a combination of the respective binding site and a T-rich promoter element. These data strongly suggest that the C-terminal domains of Abf1p and Rap1p have, at least partially, identical functions. Finally, a deletion analysis of the so far largely uncharacterized C-terminal domain of Abf1p was performed, which revealed that two regions of 50 amino acids can perform all essential Abf1p functions.

[Paralysis of the interosseous nerve by a tendinous margin of the extensor carpi radialis brevis]. / Nervus interosseus posterior-Parese durch einen sehnigen Rand des M. extensor carpi radialis brevis.

A 41-year-old woman was seen with a posterior interosseus nerve palsy. Exploration showed this to be caused by entrapment and neurotmesis of the posterior interosseus nerve under the tendinous margin of the extensor carpi radialis brevis muscle. One year after nerve reconstruction, the functional outcome was nearly normal.

Reliable treatment of pyogenic granuloma of the hand.

Pyogenic granuloma (PG) is a common skin tumour whose aetiology is unknown. There is a significant recurrence rate whatever method of treatment is used, and there are many studies in the literature on the treatment of recurrence. In our experience, the most effective way of preventing recurrence is the complete removal of the tumour using the microscope, operating in a bloodless field. Only then can the whole tumour with its supply vessels be reliably removed. 20 cases of PG on the hand, three cases in the shoulder-neck area and one case on the foot have been treated in our department over a period of 4 years. Five of these were recurrences and all involved the hand. Three of these were infected. 17 patients were followed for 3 months to 3.5 years. There were no recurrences in these patients, all of whom were operated on using the method described above.

[Diagnosis and therapy of tendovaginitis of the extensor carpi ulnaris (stenosis of the 6th extensor compartment)]. / Die Diagnostik und Therapie der Tendovaginitis des Extensor carpi ulnaris (Stenose VI. Streckerfach).

Stenosing tenosynovitis over the dorsum of the wrist in the sixth compartment is seldom mentioned in literature. We have collected 28 cases in a four-year period which demonstrate that the incidence is quite high. This condition should be considered in the differential diagnosis of pain over the dorso-ulnar aspect of the wrist. On examination firm, fusiform swelling in the sixth compartment was present. Pain was elicited by active ulnar deviation against resistance. All 28 patients had local infiltration with cortisone, but only 8 patients obtained complete relief. 18 of 20 patients had complete relief of their symptoms after surgical release of the sixth compartment. We conclude that stenosing tendovaginitis of extensor carpi ulnaris is a relatively common condition. Awareness of the syndrome allows accurate diagnosis and treatment.

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.

[An unusual case of metastasis to the soft tissues of the palm of the hand with compression of the median and ulnar nerve by kidney cancer. Case report]. / Ungewöhnlicher Fall einer Metastase in die Weichteile der Hohlhand mit Kompression des N. medianus und N. ulnaris in Folge eines Nierenkarzinoms. Fallbericht.

The incidence of secondary tumors in the hand is set slightly over 0.1%, the primary tumor localized in the lung, followed by the breast and the kidney. The authors describe a case of a renal carcinoma metastatic to the soft tissue of the palm of the hand in a patient who had undergone nephrectomy for carcinoma of the right kidney eleven years previously. The sixty-one year old female patient developed a swelling of the palm of the left hand and showed symptoms of median and ulnar nerve compression. The patient had neurosurgery because of a solitary metastatic brain tumor of the right hemisphere three months earlier and did not approve to an additional surgical intervention in the hand at that time. The decision was made to treat the tumor with a local radiation therapy. Five months later, the treatment showed no effect and the patient decided to have the operation done. Histologic examination established the diagnosis of a metastatic renal cell carcinoma. The healing was prolonged. An ulceration developed in the distal part of the wound area and healing took seven weeks. Seven months after the operation the patient was alive and well without evidence of disease. The hand showed a good function with little impairment and the symptoms of nerve compression had completely disappeared.

[Unusual course of scapho-capitate syndrome]. / Ungewöhnlicher Verlauf eines Scapho-Capitate-Syndroms.

The scapho-capitate-syndrome has been defined as combined fractures of the scaphoid and capitate with rotation of the proximal fragment of the capitate through 90 or 180 degrees. Most injuries are due to falls from heights or car accidents. Only 26 cases of the scapho-capitate fracture syndrome have been reported since 1937. In nearly one third of these cases, there was a delay of more than two weeks in diagnosis. We report a case of a young man in whom the complex injury was erroneously diagnosed as an isolated fracture of the scaphoid. The scaphoid fracture was treated by a screw and healed well. Although the patient suffered persistent pain in his wrist, the correct diagnosis was made only two years later. During revision operation we found the head of the capitate still inverted and with marked signs of avascular necrosis and destruction of the lunate cartilage. The avascular fragment was removed and substituted by a graft from the iliac crest. The capitate and lunate were fused.

[Melorheostosis of the hand (report of 2 cases)]. / Melorheostose der Hand (Ein Bericht über 2 Fälle).

Melorheostosis is a rare monostotic or polyostotic bone disease of unknown etiology. It is characterized by a slowly progressing linear hyperostosis, fibrosis of the skin and subcutaneous tissues, contractures of joints and aching pain. The lower extremities are involved much more often than the upper extremities. The distribution of the lesion usually follows sclerotomes. Bone scanning complements standard radiologic studies and permits evaluation of the extent and activity of the disease. Here we report two cases of melorheostosis. Conservative treatment was disappointing. Thus we recommend the excision of the exostosis.

[Ipsilateral inverse fibula transposition for treatment of congenital tibial pseudarthrosis]. / Die ipsilaterale inverse Fibulatransposition zur Behandlung der kongenitalen Tibiapseudarthrose.

Congenital pseudarthrosis of the tibia is one of the most challenging problems in reconstructive surgery. A wide variety of surgical methods has been utilised to treat this condition: One is the free transposition of the vascularised fibular segment to bridge the gap of pseudarthrosis. The authors report their experience in using a vascularised pedicled fibular segment of the ipsilateral fibula with reverse peroneal flow. Three patients were treated successfully. Progressive hypertrophy of the grafts without resorption was demonstrated. Within one year, all children were able to walk without an orthesis.

[A realistic practice model for learning microneural surgery without experiments on live animals]. / Ein realitätsnahes Ubungsmodell zur Erlernung der mikroneuralen Chirurgie ohne Experimente am lebenden Tier.

The increasing importance of microneurosurgery in hand and plastic surgery makes it necessary for surgeons to familiarize themselves with these techniques. In most training programs, anesthetized rats have been used to learn basic microneurosurgical techniques. Ethical considerations, the costs involved, and the legislation concerning experiments with live animals permit extensive training in microneurosurgery in only a few medical centers. This paper relates our experience with an alternative training program not involving live animals. Instead, we chose the legs of slaughtered pigs. Mono-, oligo-, and poly-fascicular nerves, structurally similar to the configurations found in human extremities, can be found in pig legs. Neurolysis, primary nerve sutures, and nerve transplantations can be practiced.

[Long-term spontaneous course of carpal instability]. / Langzeit-Spontanverläufe bei karpalen Instabilitäten.

The authors report on the natural history of 26 cases of carpal instabilities observed over a period of 25 to 74 months. Apart from the subjective criterion pain, the parameters range of motion and grip strength have been documented in the course of their development. In addition, radiographic findings have been evaluated. We confirm that carpal instabilities can lead to degenerative arthrosis. The expectation that there would be a progressive deviation from the norm of the angles between radius, scaphoid, lunate, and capitate bones measured in lateral radiographs did not prove to be true.

Training in basic microsurgical techniques without experiments involving animals.

Until recently, anaesthetised rats have been the usual material employed for learning basic microvascular and microneurosurgical techniques. However, ethical considerations, the costs involved and legislation controlling experiments with animals allow training in microsurgery for extended periods of time at a few medical centres only. This paper reports on our experience of an alternative training programme largely conducted without using live animals. As the basic material we selected legs of slaughtered pigs. According to the developing skill of the trainee, basic microsurgical techniques can be practised on arteries and veins of various sizes in these legs. To verify positive results, the vessels are subsequently perfused with human blood under pressure. The model described is particularly suited to the acquiring of skills in microneurosurgery. Mono-, oligo- and polyfascicular nerves, structurally similar to the configurations found in human extremities, are found in pig legs. The ever-increasing importance of microsurgery in modern medicine requires more and more surgeons and orthopaedists to familiarize themselves with these techniques. The model we propose for teaching and training substantially facilitate such further professional training in an efficient way, and at the same time allows a substantial reduction in the number of experiments conducted on animals.