Effect of polymer type on characteristics of buccal tablets using factorial design.

A two factor three level factorial design was used to investigate the effects of carbopol and cationic hydrophilic polymers which have a common use in buccal drug formulations. Statistical models with interaction terms were derived to evaluate influence of carbopol (X1) and chitosan (X2) on tablet disintegration (Y1) and dissolution (Y2), mechanical properties (Y3), swelling (Y4). Tablet disintegration studies were carried out using two different pH environments within buccal region pH limits and also two different commonly used dissolution methods for buccal tablets were also investigated to compare the effect of polymer type on dissolution. Polymer type and ratio affect the characteristics of the buccal tablets due to their different physicochemical behavior at buccal pH. Also significant variances between dissolution profiles for buccal tablets, using either USP Paddle or flow through cell methods were found. These results indicate that both polymer type and ratio as well as combination of them effects the drug behavior in different ways.

Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy.

INTRODUCTION: The aim of the study is to evaluate the analgesic efficiency of perioperative magnesium sulphate infusion in patients undergoing laparoscopic cholecystectomy (LC). METHODS: In a randomized, double-blind trial study, 83 patients were divided into two groups. Group MT received 50 mg/kg i.v. magnesium sulphate in 100 ml of 0.9% normal saline and Group T received the same volume of isotonic saline during the intraoperative period. The cumulative post-operative tramadol consumption was measured to assess the analgesic effect using a patient-controlled analgesia device. Pain intensities at rest and while coughing were evaluated at 0, 2, 4, 8, 12, and 24 h post-operatively. RESULTS: The pain scores in Group MT were significantly lower than Group T at 0, 4, and 12 h post-operatively. The average of visual analogue scale at rest and during cough during 24 h post-operatively was found to be statistically significant between groups. The total dose of tramadol the 24-h period in Group MT and Group T was found to be 281.34 +/- 90.82 and 317.46 +/- 129.59, respectively. CONCLUSION: Per-operative 50 mg/kg magnesium sulphate infusion is effective in reducing post-operative pain in patients undergoing LC.

Enhancement of ketoprofen bioavailability by formation of microsponge tablets.

The release of ketoprofen incorporated into modified release ketoprofen microsponge 200 mg tablets and Profenid Retard 200 mg was studied in vitro and in vivo. The formulation containing ketoprofen microsponges yielded good modified release tablets. An in vivo study was designed to evaluate the pharmacokinetic parameters and to compare them with the commercially available ketoprofen retard tablets containing the same amount of the active drug. Commercial ketoprofen retard tablets showed a more rapid absorption rate than modified release tablets and peak levels were reached within almost 3.6 h after administration. However, the new modified release tablets showed a slower absorption rate and peak levels were reached 8 h after administration.

Validated RP-hPLC method for the assay of zalcitabine in drug substance, formulated products and human serum.

A HPLC method for zalcitabine determination in bulk form, pharmaceutical dosage forms and human serum has been developed and validated. The proposed method was conducted using a reverse phase technique, and UV monitoring at 265 nm. The mobile phase consisted of methanol: 0.01 M NaH2PO4 (85:15; v/v) adjusted to pH 4.62 with 1 M NaOH. The detector response was linear in the range of 0.015-50 microg mL(-1). The limit of detection and the limit of quantification of the procedure were 0.0066 microg mL(-1) and 0.022 microg mL(-1), respectively. The retention time was 2.5 min for zalcitabine and 3.5 min for the internal standard. No interferences from tablet additives were observed and analysing tablets containing zalcitabine proved the applicability of the method. This method was also applied for the determination of zalcitabine in spiked human serum samples.

Dissolution properties of different designed and formulated salbutamol tablet dosage forms.

Pharmaceutical availability or in vitro availability is one of the aspects of drug bioavailability. Dissolution can be described best as a tool that can provide valuable information about the availability of a drug product. Dissolution test was performed on three different designed and formulated of salbutamol tablet formulations marketed in Turkey. The test methods were the paddle method and the rotating basket method described in United States Pharmacopeia. All studied formulations showed a good agreement with pharmacopeial requirements. In particular all studied commercial tablet formulations showed a quite fast release of the antiasthmatic drug. Other type of table formulations showed slow release. In order to evaluate the dissolution rates five different kinetics have been examined and the best fitting kinetics was found to be RRSBW kinetic.

Comparative dissolution testing of paracetamol commercial tablet dosage forms.

Dissolution can best be described as a tool that can provide valuable information about the availability of a drug product. In this study, nine different paracetamol tablet dosage forms available on the Turkish Drug Market have been investigated and physical controls were realized. Paddle and rotating basket apparatus methods were applied to all the formulations. In order to evaluate the dissolution rates, five different kinetics have been studied and the best fitting kinetics was found to be the Hixson-Crowell kinetics. It was found that all the preparations are in accordance with the Pharmacopeia standards.

[Diagnostic value of the tumor markers TPA-M, CYPFRA 21-1 and CEA in pleural effusion. Prospective comparison of thoracoscopic investigations in patients with pleural effusion]. / Diagnostischer Wert der Tumormarker TPA-M, CYFRA 21-1 und CEA bei Pleuraergüssen. Prospektiver Vergleich bei thorakoskopisch untersuchten Patienten mit Pleuaerguss.

The diagnostic value of tumour markers in pleural effusion is not yet clearly defined. CEA (Carcinoembryonic Antigen), CYFRA 21-1 (Cytokeratin 19-Fragment) and TPA-M, a new monoclonal-based radioimmunoassay for TPA (Tissue Polypeptide Antigen), were measured in pleural fluid and sera of 125 consecutive patients who underwent medical thoracoscopy. The group consisted of 79 patients with malignant and 45 with non-malignant pleural effusion and 1 patient without definitive diagnosis, and hence 124 patients were available for assessing the diagnostic value. In pleural fluid based on a specificity of 90% versus benign diseases the sensitivity for CEA was 52.5%; with the maximum achievable specificity of 80% for CYFRA 21-1 the sensitivity was 68% and for TPA-M with 67% the sensitivity was 67%. Based on the cut-off values for these specificities the combined use of the three tumour markers resulted in a sensitivity of 85.7% but with a lower specificity of 59.1%. There is only a limited value for tumour markers in the diagnosis of pleural effusion.

[Radiosynoviorthesis in the treatment plan of chronic inflammatory joint diseases]. / Die Radiosynovirothese im Behandlungsplan chronisch-entzündlicher Gelenkerkrankungen.

UNLABELLED: The effectiveness of radiosynovirothesis in the local treatment of chronically inflammatory joint diseases, especially rheumatoid arthritis, was evaluated. SUBJECTS AND METHODS: Follow-up examinations of 415 joints in 115 patients up to 4.5 years after intraarticular application of beta-emitting yttrium-90, rhenium-186, and erbium-169 were evaluated. The examination protocol included estimation of joint circumference, range of active joint moving capability, fist-bending power, and radiological assessment of joint destruction. Subjective assessment of pain, swelling, and joint function by the patients was evaluated by means of a score with three levels. RESULTS: The mean range of active joint moving capability increased in all joint subgroups, compared with the initial examination, with exception of ankle joints examined more than 30 months after therapy. The mean joint circumference decreased in all joint subgroups. Good to excellent results were achieved in up to 66% of joints, satisfying results in up to 21%, and no improvement or further deterioration was noted in 13% according to subjective assessment by patients themselves. Treatment proved most effective in joints with poor or no alteration in X-ray examinations. CONCLUSIONS: In the local treatment of chronically inflammatory joint diseases--especially beyond systemic drug therapy and local corticoid therapy--, radiosynoviorthesis is a low-invasive method, which may provide long-term relief of pain and swelling as well as improvement of joint function.

Diurnal variation of urinary histamine and 1-methylhistamine excretion in healthy children.

In order to establish a noninvasive method of monitoring immediate hypersensitivity reactions in children, we studied the diurnal variation of urinary histamine and 1-methylhistamine excretion and the influence of food intake in a group of 14 healthy nonatopic children (aged 2-16 years). Histamine and 1-methylhistamine in spontaneous urine samples were determined by radioimmunoassay. Mean variation of 2-h intervals was much higher for urinary histamine than for 1-methylhistamine (45% of base-line level versus 24%). There was no circadian rhythm or influence of food intake. The short half-life of histamine released into blood circulation may be the main reason for the higher variation of histamine excretion. In children, urinary 1-methylhistamine is less influenced by diurnal variation and is therefore more suited to monitor immediate hypersensitivity reactions than urinary histamine itself.

Histamine measurement in whole blood and cell supernatants. A comparative study of two different radioimmunoassays.

Histamine as an important mediator of the allergic reaction has been measured by a number of methods both in whole blood and cell supernatants after in vitro release. We compared the fluorometric histamine assay with two radioimmunoassays and studied detection limit, recovery, cross-reactivity and accuracy in buffer-based standards as well as the sensitivity after IgE-mediated in vitro release from washed cells and whole blood. Our data indicate that the double-antibody RIA (Pharmacia) can be used for studies of basophil histamine release in both whole blood and cell supernatants. Due to significant cross-reactivity to N-methyl-histamine it cannot be used for histamine determinations in plasma. The second radioimmunoassay using succinyl-glycine as an acylating reagent and monoclonal antibodies, which have been raised to acylated histamine, is the most sensitive assay without any cross-reactivity with methylhistamine.

Scintigraphic images of Swyer-James syndrome.

The Swyer-James Syndrome, first described in 1953, is a rare entity which consists of severe oligemia of one or more pulmonary lobes accompanied with bronchial deformation. Recurrent bronchial infections in childhood are believed to be the cause, leading to obliteration of small airways, alveolar overdistension and, ultimately, the destructive changes characteristic of emphysema. Secondary vascular alterations occur resulting in oligemia of the afflicted lobe. The clinical presentation is variable ranging from the totally asymptomatic patient to dyspnea on exertion or recurrent lower respiratory tract infections. The physical examination may reveal hyperresonance over the affected area, restricted chest expansion on one side, or occasionally rales on auscultation. Radiological findings are characteristic and include a pronounced one sided hyperlucency of the lung (due to oligemia), a mediastinal shift toward the affected side on inspiration, a small ipsilateral hilus, and bronchial deformities as disclosed by bronchography. Another radiologic feature, described as a "sine quanon" condition for diagnosis by Fraser and Paré is the development of air trapping during expiration. Various diagnostic modalities including roentgenography, bronchoscopy, bronchography, angiography and radionuclide imaging are necessary to obtain the diagnosis.

Fluoroimmunoassay: an alternative to radioimmunoassay?

Fluoroimmunoassays appear to be an alternative to conventional radioimmunoassays and immunoradiometric assays because of the high specific activity of their label, thus promising high sensitivity and excellent precision. According to IFCC recommendations for the assessment of new laboratory methods, we evaluated precision, accuracy, linearity, lower detection limit and normal reference ranges of commercially available immunofluorometric assays of alpha-fetoprotein, choriongonadotropin and thyrotropin. In addition, thyrotropin content in sera of 147 patients was measured by immunofluorometric assay. Analysis of immunofluorometric assays gained performance data comparable to those of currently used immunoradiometric assays. Regression studies performed against currently employed methods showed accuracy of all three immunofluorometric assays. Results of immunofluorometric assay for thyrotropin demonstrated that sera of hyperthyroid subjects were distinguished from those of euthyroid subjects from basal thyrotropin alone. We conclude that immunofluorometric assays are an alternative to immunoradiometric assays which anybody concerned about the future of in vitro nuclear medicine should be aware of.

Metastatic pulmonary calcification in a patient with nonsecretory multiple myeloma.

A case of nonsecretory multiple myeloma is presented. Radiological findings and bone marrow examination provided the diagnosis. Bone scintigraphy showed metastatic pulmonary calcification, thus demonstrating the potential superiority to any other routine diagnostic modality in detection of visceral calcification.

[Comparative scintigraphic analysis of 99mTc aerosol inhalation and 81m Kr ventilation in chronic obstructive bronchial disease]. / Vergleichende szintigraphische Analyse der 99mTc-Aerosol-Inhalation und der 81mKr-Ventilation bei chronisch obstruktiver Bronchialerkrankung.

The usefulness of 99mTc-labelled serum albumin aerosol as a ventilation agent was compared to that of 81mKr gas in normal subjects and in patients with a wide range of pathological pulmonary function. In addition to visual analysis of the scintigrams, lung activity distribution was quantified by an index. In healthy subjects aerosol distribution was very similar to that of 81mKr gas. In patients with persistent obstruction of bronchial air flow, the aerosol tended to penetrate less well than 81mKr gas to the lung periphery and to show a more uneven pulmonary tracer distribution. Consequently the 81mKr gas technique resulted in underestimating bronchial obstructive defects compared with the radioaerosol method. The results indicate that unlike 81mKr gas imaging, small-particle aerosol scintigraphy provides a useful diagnostic technique for the detection of even mild air flow obstructions.

[Diagnosis of renovascular hypertension by intravenous digital subtraction angiography and renal sequential scintigraphy]. / Die Abklrung der renovaskulären Hypertonie mittels intravenöser digitaler Subtraktions-angiographie und Nierensequenzszintigraphie.

Intravenous digital subtraction angiography (DSA) and 131J-hippuran clearance (NSS) were evaluated in 113 patients, both methods were made as screening tests for renovascular hypertension. In 9 examinations DSA was not diagnostic, in 18 patients arterial wall lesions were found. The dynamic renal imaging with hippuran showed alterations in 86 patients, 2 patients with renal arterial stenosis had normal findings. Combination of both methods yields good results in estimation of the haemodynamic significance of a renal arterial narrowing.

[Diagnostic value of sacroiliac-joint scintigraphy in acute iridocyclitis]. / Zur Wertigkeit der szintigraphischen Untersuchung der Iliosakralgelenke bei der akuten Iridozyklitis.

The association between acute iridocyclitis (a.i.) and sacroiliitis/ankylosing spondylitis is well known. Since bone scintigraphy is a sensitive method of detecting sacroiliitis before radiologic evidence of this condition appears, we examined the role of scintiscanning in the investigation of sacroiliitis in patients with a.i. The sacroiliac-joint/sacrum ratio was determined in 30 control subjects and in 21 patients with a.i., who showed no radiologic signs of sacroiliitis. No discrimination between patients with a.i. and control subjects was obtained by scintigraphy, neither did we find any difference in the mean sacroiliac-joint/sacrum ratios between HLA-B-27-positive and HLA-B-27-negative individuals with a.i. This study does not support the claim that patients with a.i. often suffer from clinically and radiologically silent sacroiliitis which would be detected only by scintigraphy. According to our results, regular scintigraphic examinations of the sacroiliac joint in all patients with a.i. are not indicated.

Optimizing renal DMSA-scintigraphy with 7-pinhole collimator.

Multiple pinhole emission tomographic imaging techniques are currently being applied to imaging of organs of a limited size. The purpose of this study was to evaluate the feasibility of this technique in kidney imaging with Tc99m-DMSA. A 7-pinhole collimator having 4.5 mm. pinhole apertures was used in conjunction with a widefield camera. Left and right kidney were imaged separately. Twelve small renal cysts with a diameter of 1 to 3.5 cm. verified by US or CAT were investigated by 7-pinhole and planar scintigraphy. Eight of 12 renal cysts were identified by 7-pinhole scintigraphy whereas only one cyst was seen by planar scintigraphy. The borderline of cysts detection was 1.5 cm. in 7-pinhole tomography. Basing on these comparative studies and experiences on many patient investigations it seems reasonable to perform renal scintigraphy with 7-pinhole tomography in a routine manner.

[Ankylosing spondylitis in women: comparison of scintigraphic results with clinical and roentgenologic findings]. / Die Spondylitis ankylosans beim weiblichen Geschlecht: Ein Vergleich szintigraphischer Ergebnisse mit klinischen und röntgenologischen Befunden.

Since ankylosing spondylitis (S.a.) tends to be milder and less progressive in women than in men, there are great difficulties in diagnosing S.a. in female patients. The role of scintiscanning for investigation of S.a. in women is discussed by few examiners only, especially there are no investigations of quantitative sacroiliac scintigraphy in large groups of female patients. Quantitative sacroiliac scintigraphy was performed in 19 female patients with S.a. and in 30 control subjects. The sacroiliac/sacrum ratio (Index ISG/sacrum) was calculated. Significantly increased uptakes were found in the patient group compared with the controls. Especially in the early periods of S.a. the activity index was highest. When history and physical examination lead to a suspicion of S.a. and there is no verification by roentgenographic studies, sacroiliac joint scintigraphy is indicated. If clinical and laboratory findings are respected in each patient, quantitative sacroiliac scintigraphy is useful for the early diagnosis of S.a. in female patients.