Exploration of Novel Co-processed Multifunctional Diluent for the Development of Tablet Dosage Form.

The aim of this investigation was to develop a novel multifunctional co-processed diluent consisting of microcrystalline cellulose (Avicel PH 102), crospovidone (Polyplasdone XL) and polyethylene glycol 4000. Colloidal silicon dioxide and talc were also incorporated as minor components in the diluent to improve tableting properties. Melt granulation was adopted for preparation of co-processed diluent. Percentage of Avicel PH 102, Polyplasdone XL and polyethylene glycol 4000 were selected as independent variables and disintegration time was chosen as a dependent variable in simplex lattice design. The co-processed diluent was characterised for angle of repose, bulk density, tapped density, Carr's index, percentage of fines and dilution potential study. Acetaminophen and metformin were used as poorly compressible model drugs for preparation of tablets. The blend of granules of drug and extra-granular co-processed diluent exhibited better flow as compared to the blend of drug granules and physical mixture of diluents blend. The diluent exhibited satisfactory tableting properties. The tablets exhibited fairly rapid drug release. In conclusion, melt granulation is proposed as a method of preparing co-processed diluent. The concept can be used to bypass patents on excipient manufacturing.

Fabrication and Evaluation of Bi-layer Tablet Containing Conventional Paracetamol and Modified Release Diclofenac Sodium.

The objectives of present investigation were to achieve immediate release of paracetamol and tailored release of diclofenac sodium from bi-layer tablets. A 2(3) full factorial design was adopted using the amount of polyethylene glycol, microcrystalline cellulose and crospovidone as independent variables for fabricating paracetamol tablets. Diclofenac sodium tablets were prepared using hydroxypropyl methylcellulose as a matrixing agent. The results of analysis of variance showed that the friability of paracetamol was distinctly influenced by the formulation variables. The in vitro drug release behaviour of diclofenac tablets was compared with a marketed formulation. The optimized formulations of paracetamol and diclofenac sodium were used for manufacturing of bi-layer tablets. The bi-layer tablets showed immediate release of paracetamol and modified release of diclofenac.

Preparation and evaluation of soft gellan gum gel containing paracetamol.

The objective of this study was to develop soft paracetamol gel using gellan gum as a gelling agent and sodium citrate as a source of cation. Different batches were prepared using three different concentrations of gellan gum (0.1, 0.3, and 0.5%), each with two different sodium citrate concentrations (0.3 and 0.5%). The consistency of the paracetamol gel was dependent on the concentration of gellan gum, sodium citrate and co-solute. The results of dissolution study of soft gel containing 0.3% gellan gum and 0.3% sodium citrate revealed that paracetamol was completely released in 30 min. Polyethylene glycol 400 worked as a solubilizer for paracetamol. All the gels possessed acceptable sensory characteristics when evaluated by human volunteers. Short term stability study carried out for four weeks at different temperatures revealed no considerable changes in performance characteristics of developed optimized formulation.

Prolonged postoperative analgesia for arthrolysis of the elbow joint.

We describe the provision of postoperative analgesia for 6 days for a patient undergoing arthrolysis of the elbow joint. Mobilization of the elbow immediately after operation is essential to maintain movement achieved with surgery and this can be obtained only with effective pain relief. We used continuous infusion of 0.125% bupivacaine and subsequent addition of fentanyl to the infusate, via a catheter inserted supraclavicularly into the sheath of the brachial plexus.

Comparison of fentanyl and halothane supplementation to general anaesthesia on the stress response to upper abdominal surgery.

The stress response to surgery and anaesthesia was studied in 20 patients undergoing cholecystectomy or vagotomy and pyloroplasty. Patients were anaesthetized with thiopentone and nitrous oxide; 10 patients received supplements of 0.5-1.5% halothane and the others fentanyl (mean 17 micrograms kg-1). The plasma concentrations of cortisol and glucose increased in both groups during surgery and remained greater than baseline immediately following recovery of consciousness. The hyperglycaemic response in the halothane group was greater than in the fentanyl group. Plasma noradrenaline concentrations increased in the group receiving halothane, but did not increase significantly in the group receiving fentanyl.

Changes in iron metabolism following surgery.

Studies of iron metabolism were made in 24 patients following surgery under general anaesthesia. No postoperative complications occurred. There was a marked fall in serum iron in all patients on the first postoperative day (P less than 0.001) which remained significantly depressed even at the seventh postoperative day. The total iron binding capacity fell progressively to reach the lowest levels on the third postoperative day, returning to normal levels by the end of the study. Serum ferritin concentration rose significantly in a reciprocal pattern to the changes in serum iron. This study highlights the limitation of iron studies in peripheral blood in postoperative patients.

Effect of certain anaesthetic agents on the activity of rat hepatic delta-aminolaevulinate synthase.

The activity of delta-aminolaevulinic acid synthase (E.C.2.3.1.37) (the rate-limiting enzyme for haem and porphyrin biosynthesis) has been measured in the rat liver after the repeated administration of anaesthetic agents in vivo. The activity of the enzyme was increased by Althesin, chlordiazepoxide, enflurane, etomidate, lignocaine, methohexitone, methoxyflurane, pentazocine and thiopentone and decreased by procaine. No significant changes in activity occurred after the administration of amethocaine, atropine, bupivacaine, diazepam, droperidol, halothane, ketamine, morphine, nitrous oxide, pethidine, phenoperidine, prilocaine and propanidid. It is suggested that those anaesthetic agents which induced activity of the enzyme should not be administered to patients with an acute porphyria.

Screening for malignant hyperpyrexia.

The methods used to screen patients for malignant hyperpyrexia at present are not sufficiently accurate. This paper reports more specific methods of detecting patients liable to develop malignant hyperpyrexia. A motor-point muscle biopsy is performed for histopathological examination and to detect muscle contracture in vitro after exposure to halothane and suxamethonium.