Lyophilization of polyethylene glycol mixtures

Lyophilization of cosolvent systems may be a beneficial way of enhancing both physical and chemical stability of a drug product. The objective of this research is to establish whether cosolvent systems commonly used in the formulation of poorly water-soluble drugs can be successfully lyophilized. Polyethylene glycol (PEG) 400 was selected because it is widely used and can be easily frozen. The addition of PEG 400 to commonly used bulking agents, such as mannitol, sucrose, or polyvinylpyrrolidone, caused a significant change in the thermal properties of the bulking agents as observed by modulated differential scanning calorimetry. In addition, PEG 8000 was evaluated as a bulking agent because it also can function as a cosolvent in solution and forms an acceptable cake after lyophilization. Addition of PEG 400 to PEG 8000 caused negligible changes in the thermogram of this bulking agent. Surprisingly, the combination of PEG 8000 and PEG 400 forms a solid lyophilized cake. The current system can be best described as the lyophilization of a miscible solution of PEG 8000 and PEG 400 resulting in a lyophile that has a crystalline structure of PEG 8000 which is able to support PEG 400.     

Tumor like swellings arising from Hoffa's fat pad: A report of three patients

We report three rare cases of tumor-like conditions arising from Hoffa''s fat pad (HFP). Patients were having persistent knee pain, the cause of which was not diagnosed by the general physician, and then were referred to us for knee pain. Magnetic resonance imaging revealed the lesions to be arising from HFP (ganglion cysts and hemangioma), as was suggested by clinical findings. Anatomy, pathology, and radiological features of the Hoffa''s disease are described here to increase awareness in orthopedic community of this rare but interesting disease which is often misdiagnosed as meniscal pathology. These cases illustrate that increased cognizance can facilitate timely intervention which will prevent morbidity of the patient.     

Concurrent use of intranasal and orally inhaled fluticasone propionate does not affect hypothalamic-pituitary-adrenal-axis function.

Two double-blind, randomized, placebo-controlled, parallel group safety and efficacy studies included evaluation of the hypothalamic-pituitary-adrenal (HPA)-axis effects of concurrent treatment with intranasal and orally inhaled fluticasone propionate (FP). In the first study, patients with asthma who were > or =12 years of age were assigned randomly to receive twice-daily doses (either 88 or 220 microg) of orally inhaled FP delivered from a metered-dose inhaler (MDI). In the second study, patients were assigned randomly to receive either orally inhaled FP 250 microg or orally inhaled FP 250 microg/salmeterol 50 microg delivered via the Diskus device. In both studies, patients with rhinitis were allowed to continue the use of intranasal FP at their usual dosing. Treatment periods were 26 weeks and 12 weeks for the MDI and Diskus studies, respectively. HPA-axis effects were assessed using response to short cosyntropin stimulation testing. The number and percentage of patients with an abnormal cortisol response, defined as a morning plasma cortisol of <5 microg/dL, a poststimulation peak of <18 microg/dL, or a poststimulation rise of <7 microg/dL, were summarized in two subgroups: patients who used intranasal FP and those who did not. The concurrent administration of intranasal FP and orally inhaled FP via an MDI or Diskus or via Diskus with salmeterol was not associated with HPA-axis effects compared with orally inhaled FP alone. The results of these two studies suggest that concurrent use of intranasal FP with orally inhaled FP administered via MDI or Diskus for treatment of comorbid rhinitis and asthma does not increase the risk of HPA-axis abnormalities.     

Evidence for abnormal granulosa cell responsiveness to follicle-stimulating hormone in women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) undergoing ovulation induction appear to be extremely sensitive to gonadotropin stimulation and at increased risk for ovarian hyperstimulation syndrome. To determine granulosa cell responsiveness to recombinant human FSH (r-hFSH), dose-response studies were conducted in 16 individual PCOS patients and 7 normal women. Each subject received an iv injection of r-hFSH at doses of 0, 37.5, 75, or 150 IU in a randomized fashion on four separate occasions. Blood samples were obtained at frequent intervals before and for 24 h after r-hFSH administration for measurement of gonadotropins and steroid hormones. Our results showed that administration of r-hFSH produced instantaneous and equivalent dose-related increases in serum FSH in PCOS and normal women, which were followed by similar exponential decreases to baseline levels within 24 h in both groups. In PCOS subjects, the peak mean incremental response of serum estradiol (E(2)) to 150 IU of r-hFSH was 1.8-fold greater (P < 0.0001) and considerably accelerated compared with that found in normal women. In contrast, E(2) responses to 37.5 IU and 75 IU were similar between groups. Regression analysis of maximal E(2) concentrations in response to r-hFSH in each individual subject revealed that the slope of the linear trend line in the group of women with PCOS (r = 0.82) was significantly greater (P < 0.01) than that of normal controls (r = 0.71). The time-course of response revealed that in PCOS women, increases of E(2) were not sustained, compared with those of normal controls, because peak concentrations were followed by an estimated 40% decrement in circulating levels, whereas E(2) levels in normal women persisted for 24 h after reaching maximal values. These findings indicate that women with PCOS exhibit a significantly greater capacity for E(2) production in response to iv r-hFSH, compared with normal women. In PCOS, E(2) production was relatively transient because after peak concentrations a marked decline was detected at each dose, unlike normal women who exhibited persistent elevations of E(2) for up to 24 h. That this distinction was dose-dependent supports the concept of an FSH dose-response threshold, beyond which PCOS but not normal women are susceptible to ovarian hyperresponsiveness.