Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

BACKGROUND: Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. OBJECTIVES: To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. METHODS: Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. RESULTS: The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. CONCLUSION: Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

Quantification of dexamethasone and corticosterone in rat biofluids and fetal tissue using highly sensitive analytical methods: assay validation and application to a pharmacokinetic study.

A sensitive, specific, accurate and precise LC/MS/MS method was developed for the simultaneous measurement of dexamethasone and corticosterone in rat plasma. The method was extended to dexamethasone analysis in rat plasma ultrafiltrate and fetal tissues. Samples were processed using SPE involving Oasis HLB cartridges, which offered complete extraction recovery for the analytes. Samples were subsequently analyzed using LC/MS/MS. A structurally related corticosteroid, prednisolone, was used as the internal standard. Using a 500 microL plasma sample, limits of quantification of 0.2 and 2.0 ng/mL were achievable for dexamethasone and corticosterone. This level of sensitivity allowed characterization of maternal/fetal dexamethasone profiles after administration of multiple doses of dexamethasone sodium phosphate to rats. However, this sensitivity was not satisfactory for corticosterone during pharmacokinetic studies involving dexamethasone due to its strong adrenosuppressive effect. This led us to investigate the suitability of a commercially available radioimmunoassay kit, which through extensive testing and minor modifications was found to offer extremely sensitive, specific, accurate and precise analysis of corticosterone. Knowledge of the steroid profiles captured using these highly sensitive analytical tools may potentially help in the optimization of corticosteroid therapy during pregnancy.

Adverse events of standardized regimens of corticosteroids for prophylaxis and treatment of nerve function impairment in leprosy: results from the 'TRIPOD' trials.

Reactions in leprosy causing nerve function impairment (NFI) are increasingly treated with standardized regimens of corticosteroids, often under field conditions. Safety concerns led to an assessment of adverse events of corticosteroids, based on data of three trials studying prevention of NFI (the TRIPOD study). A multicentre, randomized, double-blind placebo-controlled trial was conducted in leprosy control programmes in Nepal and Bangladesh. Treatment was with prednisolone according to fixed schedules for 16 weeks, starting in one trial with 20 mg/day (prophylactic regimen: total dosage 1.96 g) and in the other two trials with 40 mg/day (therapeutic regimen: total dosage 2.52 g). Minor adverse events were defined as moon face, fungal infections, acne, and gastric pain requiring antacid. Major adverse events were defined as psychosis, peptic ulcer, glaucoma, cataract, diabetes and hypertension. Also, the occurrence of infected plantar, palmar, and corneal ulceration was monitored, together with occurrence of TB. Considering all three trials together, minor adverse events were observed in 130/815 patients (16%). Of these, 51/414 (12%) were in the placebo group and 79/401 (20%) in the prednisolone group. The relative risk for minor adverse events in the prednisolone group was 1.6 (P = 0.004). Adverse events with a significantly increased risk were acne, fungal infections and gastric pain. Major adverse events were observed in 15/815 patients (2%); 7/414 (2%) in the placebo group and 8/401 (2%) in the prednisolone group. No major adverse events had a significantly increased risk in the prednisolone arm of the trials. No cases of TB were observed in 300 patients who could be followed-up for 24 months. Standardized regimens of corticosteroids for both prophylaxis and treatment of reactions and NFI in leprosy under field conditions in developing countries are safe when a standard pre-treatment examination is performed, treatment for minor conditions can be carried out by field staff, referral for specialized medical care is possible, and sufficient follow-up is done during and after treatment.

Combined prednisolone and intravenous immunoglobulin treatment for acquired factor VIII inhibitors: a 2-year review.

Acquired inhibitors to factor VIII (FVIII) are rare, but life-threatening in up to 22% of cases. The optimal therapy for suppression of these inhibitors remains unclear. Prednisolone is the mainstay of therapy, producing responses in approximately 30% of cases. Intravenous immunoglobulin (IVIg) has a similar response rate, but a more rapid effect. We report the results of prednisolone 1 mg kg(-1) combined with IVIg 2 g kg(-1) in divided doses as first-line therapy in seven consecutive patients with acquired FVIII inhibitors. All patients were bleeding at the time of diagnosis with prolonged activated partial thromboplastin time. There were four complete responses, one partial response, one nonresponse and one with an inadequate follow-up for assessment of response, giving an overall response rate of 71%. In all complete responders the inhibitor declined rapidly and was undetectable by day 21 from start of treatment. Therapy was well tolerated and responses have been maintained off treatment for 2-8 months. This is a safe, well-tolerated rapidly acting regimen with good response rates.

Acquired haemophilia: experiences with a standardized approach.

Acquired haemophilia is a rare, life-threatening, acquired bleeding diathesis. No general consensus exists on the best therapeutic approach. We report on the standardized approach at our institution evaluated in ten patients with acquired haemophilia. Factor VIII inhibitors were found in all patients, activities ranging from 1 to 648 Bethesda units (BU). Eight of the ten patients presented with severe bleeding. Two patients died during the acute phase, one from intracranial bleeding and one due to Mycoplasma pneumonia. One patient with mild bleeding was treated with immunosuppression alone. Two patients with factor VIII inhibitor activities below 5 BU were started on factor VIII concentrate therapy. Therapy was successful in one and was changed to recombinant human activated factor VII infusion (rFVIIa) in the other, owing to insufficient factor VIII recovery. Six patients with factor VIII inhibitor activities above 5 BU were started on activated prothrombin complex concentrate (APCC) therapy. APCC treatment was successful initially in all six patients and was changed to rFVIIa infusion in one for rebleeding. One patient did not receive any specific therapy. Immunosuppression with prednisolone (2 mg kg(-1)) was begun in nine patients and was continued with cyclophosphamide (2 mg kg(-1)) in six. A complete remission of the acquired haemophilia was found in seven of the eight patients surviving the acute phase, one had a partial remission. All patients with acquired haemophilia could be managed effectively following our standardized approach. Routine administration of immunosuppression was associated with high inhibitor elimination rates.

[Prednisolone Sodium Phosphate Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material for prednisolone sodium phosphate was examined for the preparation of the "Prednisolone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: pH, 7.9; optical rotation, [alpha]D20 = +98.0 degrees; UV spectrum, lambda max of 248 nm and specific absorbance in ethanol at 248 nm = 306.7; IR spectrum, same as that of the Prednisolone Sodium Phosphate Reference Standard (Control 892); thin-layer chromatography, five impurities were detected at 200 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 3.7%; residual solvent, 0.0% (ethanol) and 0.0% (hexane); loss on drying, 2.7%. Based on the above results, the raw material was authorized as the Prednisolone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.

[Prednisolone Reference Standard (Control 971) of National Institute of Health Sciences].

The raw material of prednisolone was examined for the preparation of the "Prednisolone Reference Standard (Control 971)". Analytical data obtained were as follows: melting point, 238.4 degrees C (decomposition); infrared spectrum, the same as that of the Prednisolone Reference Standard (Control 911); UV spectrum, lambda max = 243 nm; specific absorbance, E1 cm 1% (243 nm) = 414.8; loss on drying, 0.06%; thin-layer chromatography, one impurity was detected; high-performance liquid chromatography (HPLC), 4 to 5 impurities were detected and the total amount was estimated to be about 0.51%; assay by HPLC, 100.6%. Based on the above results, the raw material was authorized as the Prednisolone Reference Standard (Control 971) of National Institute of Health Sciences.

Sterile idiopathic pedal panniculitis in the German shepherd dog--clinical presentation and response to treatment of four cases.

Four cases of sterile idiopathic pedal panniculitis are described in the German shepherd dog. All the dogs presented with characteristic clinical signs of localised panniculitis dorsal to the midline of the carpal or tarsal pads of one or more legs. Diagnostic procedures did not identify a cause for the panniculitis and none of the cases had a history of penetrating foreign bodies. All cases failed to respond to antibiotic therapy but cases failed to respond to antibiotic therapy but did respond to anti-inflammatory doses of prednisone. The lesions in three dogs relapsed once the levels of steroids were reduced. However, in two of the cases oral vitamin E therapy at a dose of 300 iu twice daily acted in a steroid sparing capacity. In a fourth case, vitamin E acted to control the clinical signs without steroid therapy.

Evaluation of different ovarian stimulation protocols for in vitro fertilization.

In this study we evaluated retrospectively the efficacy of five different ovarian stimulation protocols in an in vitro fertilization program, in which 512 women were involved. Ovulation was induced by the following protocols: group I (271 cycles): buserelin short protocol (1 mg/day, intranasally) with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG); group II (45 cycles): buserelin (short protocol) with pure follicle stimulating hormone (p-FSH)/hMG/hCG; group III (24 cycles): clomiphene citrate (100 mg/day) with hMG/hCG; group IV (122 cycles): hMG (3 ampules/day) and hCG; group V (113 cycles): hMG/hCG and prednisolone (7.5 mg/day) after cycle programming with oral contraceptives. The lowest cancellation rate (3.3%) was noted in group I, followed by group V (9.7%). The highest number of follicles was observed in groups I (8.3 +/- 0.3; mean +/- SEM) and V (7.8 +/- 0.5). Also, more oocytes were retrieved in group I (7.2 +/- 0.3, p < 0.001), which were of good quality based on oocyte maturity as well as on the fertilization rate, and more embryos (4.5 +/- 0.3, p < 0.05) were developed. The correlation between estradiol and the total follicular volume on the day of hCG administration was also examined in the five groups. The best correlation (r = 0.6502) was found in group I, followed by group V (r = 0.5810). Significant differences were observed in the five groups with regard to the number of hMG ampules administered (p < 0.0001, F = 15.393) and the stimulation days (p < 0.0001, F = 35.32). Sixty-six clinical pregnancies were achieved: 37 (17.5%) in group I, seven (25.9%) in group II, one (10%) in group III, ten (15.6%) in group IV and 11 (15.5%) in group V (differences were not statistically significant). In conclusion, all five protocols were satisfactory in ovarian stimulation for in vitro fertilization, and gonadotropin releasing hormone (GnRH) analogs seemed to be more advantageous by reducing the cancellation rate, enhancing the number of oocytes retrieved and embryos developed and by improving the pregnancy rates.

[Prednisolone acetate reference standard (Control 941) of the National Institute of Health Sciences].

The raw material for prednisolone acetate was tested for preparation of the "Prednisolone Acetate Reference Standard (Control 941)". Analytical data obtained were as follows: melting point, 237.5 degrees C (decomposition); UV and infrared spectra, the same as those for JP Prednisolone Acetate Reference Standard (Control 903), respectively; specific absorbance at lambda max E1%1cm = 379; optical rotation, [alpha]20D = +115.2 degrees; thin-layer chromatography and high-performance liquid chromatography (HPLC), no impurities were detected, respectively; assay, 100.8% by HPLC. Based on the above results, the candidate material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).

[Prednisolone reference standard (Control 911) of the National Institute of Hygienic Sciences].

Prednisolone was tested for preparation of the "Prednisolone Reference Standard (Control 911)". The quality of raw material was examined and compared with the previous Reference Standard (Control 872). Analytical data obtained were as follows: loss on drying, 0.10%; melting point, 233.2 degrees C (decomposition); optical rotation, [alpha]20D+98.77 degrees; UV spectrum, lambda max = 243nm; absorptivity, E1%1cm (243nm) = 413.5; IR spectrum, 1711, 1612, 1110, 888cm-1; one impurity was detected by thin-layer chromatography and high-performance liquid chromatography (HPLC), respectively; assay, 100.1% by HPLC. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 911).

Etoposide, ifosfamide and methotrexate combination chemotherapy in patients with aggressive non-Hodgkin's lymphoma after failure of the LNH 84 regimen.

We assessed the efficacy of an etoposide, ifosfamide and methotrexate combination therapy (VIM) in 24 patients failing the LNH 84 protocol. Eight of these patients were refractory to the LNH 84 induction regimen, 10 were partial responders and the six remaining attained complete response after LNH 84 induction but relapsed during consolidation therapy or after completing the whole programme. Twenty-three patients were evaluable for response. The VIM regimen provided a 43 per cent complete response rate and an additional 17 per cent partial response rate. The complete response rate was particularly high (67 per cent) in the group of patients who were partial responders to LNH 84 induction treatment. Of the 10 complete responders, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 27 to 60 months. Overall VIM was well tolerated. Myelotoxicity was the most common side-effect. Infections with fever were observed in 8 per cent of the VIM courses. This study demonstrates that a complete response and a long survival can be obtained in patients after failure of a high-dose doxorubicin containing front-line treatment.

[Prednisolone Acetate Reference Standard (Control 901) of the National Institute of Hygienic Sciences].

Prednisolone Acetate Reference Standard (Control 901) for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 236 degrees C (decomposition); IR spectrum was same as that of JP RS of prednisolone acetate; absorptivity at 243 nm E1%lcm = 379; optical rotation [alpha]20D = +113.0 degrees; no impurity was detected by TLC, but a small amount of two impurities was found by HPLC analysis; assay by HPLC against the JP RS 100.2%. Based on the above results, this raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.

[Prednisolone Reference Standard of National Institute of Hygienic Sciences].

Prednisolone reference standard for the Japanese Pharmacopoeia was prepared. The quality of raw material was examined and compared with the previous reference standard (Control 821). Analytical data for this substance were as follows: loss on drying, 0.04%; melting point, 234.1 degrees C (decomposition); optical rotation, [alpha] 20D + 100.2 degrees; UV spectrum, lambda max = 243 nm; absorptivity, E1%1cm (243 nm) = 415; IR spectrum, 1711, 1655, 1612, 1111, 899 cm-1; one impurity was detected by TLC and high-performance liquid chromatography (HPLC), respectively; assay by HPLC, 100.1%. Based on the above results, this raw material was authorized as the Reference Standard of National Institute of Hygienic Sciences.

Liquid chromatographic determination of prednisolone in tablets and bulk drugs: interlaboratory study.

A normal phase liquid chromatographic (LC) method for the determination of prednisolone in tablets and bulk drugs was studied by 7 analysts. An LC system, consisting of a methanol-water-ethylene dichloride-acetic acid mobile phase and a silica column, was used to analyze bulk drugs, individual tablets, and composite samples. Analysts were supplied with 16 samples, including simulated formulations, composites of commercial tablets, intact tablets, and bulk drug substances. Results agreed with those obtained by the author. The coefficients of variation of the analysts' results ranged from 1.34% for bulk drugs to 2.14% for tablet composites. The LC method is suggested as an alternative to the official AOAC and USP XX blue tetrazolium colorimetric methods.

An evaluation of prednisolone as a routine adjunct to the treatment of T. rhodesiense.

The purpose of this exercise was to evaluate the efficacy of a cortico-steroid in protecting the patient suffering from Rhodesian sleeping sickness from the complications of melarsoprol treatment. It is quite clearly shown that prednisolone was not effective in offering protection against the most serious treatment problem, encephalopathy. The apparent total success of the steroid in protecting the first group from the less severe treatment complications and in minimising early death need to be interpreted with some scepticism due to the smallness of the series. Nevertheless, it does help to substantiate the observations of others that in the case of the moribund patient, the immediate use of steroids might be life saving. On the basis of these findings the routine use of prednisolone as an adjunct to the treatment of T. rhodesiense was discontinued. The use of a cortico-steroid has been continued, however, as treatment for reactive encephalopathy, arsenical dermatitis and arsenical enteritis and with patients who are moribund on admission.