Advances in coamorphous drug delivery systems

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, and performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.

Flow cytometry based chronologic analysis of surface glycoproteins of resting and stimulated platelets in normal individuals

To evaluate the effect of timed incubation on the activation dependent glycoproteins on the surface of unfixed platelets after stimulation with adenosine diphosphate [ADP]. A total of 32 normal subjects were recruited in this study. CBC, Hb A1C, fasting and random blood sugar, urea, creatinine, cholesterol, triglycerides, high density as well as low density lipoproteins were determined. Flow cytometric analysis of platelets was done using FACSCalibur [BD Bioscience]. Two sets of CD markers i.e. platelets CD41and CD61 and CD63 and CD 62p were studied during resting state and after stimulation with ADP. Mean +/- SD values of CD41 and CD61 surface markers of resting and stimulated platelets showed no statistical difference; p value being 0.198 and 0.486 respectively. Comparison of CD41 and CD61 markers at 20 minutes Vs 2 hrs, 20 minutes Vs 3 hrs and 2 hrs Vs 3 hrs didn't show any significant difference after stimulation with ADP. This indicates that these markers remain stable and they are not affected by incubation for up to 3 hours. Activation of platelets with ADP resulted in an increase in the number of CD63 and CD62p positive platelets with a p value of 0.001. Activity of CD63 remained high while that of CD62p progressively decreased after incubation for 2 and 3 hours. CD63 is an ideal marker to evaluate functional status of the platelets while CD62p positivity, though it increases after activation, cannot be used alone as a marker of platelet activation because its positivity decreases with the passage of time. Changes in CD62p positivity when considered in conjunction with increased CD63 positivity lend support to the presence of increased number of activated platelets in the peripheral blood

Molecular genetics of beta-thalassaemia syndrome in Pakistan

This molecular genetics study was conducted in Karachi, Pakistan from 2004 to 2006 to provide guidelines for prenatal diagnosis programmes in the country. Blood samples of patients with beta-thalassaemia minor [n = 200] and beta-thalassaemia major [n = 150] were collected from hospitals, transfusion centres and diagnostic laboratories from different districts of Karachi, representing 5 major ethnic groups. Molecular analysis revealed 11 genetic mutations of the beta-thalassaemia gene, among which 5 mutations accounted for 88% of the total beta-thalassaemia genes identified [IVS-1-5 [G-C], Fr 8/9 [+G], Fr 41/42 [-TTCT], IVS-1-1 [G-T] and Del 619]. Other mutations identified were: CAP+1, IVS-II-1 [G-A], Cd 5 [-CT], Cd 15 [G-A], Cd 16 and Cd 30

Maximum tolerable dose of cyclophosphamide and azathioprine in Pakistani patients with primary renal disease

Objective: The immunosuppressive regimens, at present, mainly rely on western guidelines that were derived from studies conducted in western populations. No such study exists for South Asian population, which is home to almost two billion people different in both genetics and environment from west. Locally derived thresholds for side effects markedly different from western figures may warrant re-adjustment of current local immunosuppressive regimens that are at present based largely on western guidelines. In order to define optimum dose for Cyclophosphamide [CYC] and Azathioprine [AZA] based immunosuppressive therapy, we conducted this study to find out maximum tolerable doses of azathioprine [AZA] and cyclophosphamide [CYC] beyond which neutropenia and thrombocytepenia are most likely to occur in patients with primary renal pathology

Method: Patients with systemic vasculitis and idiopathic glomerulonephritis who were on CYC and AZA were identified through review of medical records at a tertiary care hospital in Pakistan [The Aga Khan University Hospital, Karachi]. Patients were categorized under three principal diagnosis i.e. systemic lupus erythematosus [SLE], primary [idiopathic] glomerulonephritis [GN] and Wegener's granulomatosis [WG]. The Receiver Operating Curve [ROC] was used to calculate the maximum tolerable dose for both CYC and AZA

Results: We identified 94 patients aged 6-82 years [median 44.5 years] with primary renal disease [Wegener's granulomatosis n=13, Systemic lupus erythematosis n=62 and idiopathic glomerulonephritis n=19] who received CYC or AZA. Of these 94 patients, 36.2% [n=34] received CYC and 63.8% [n=60] received AZA. The mean dose of CYC was 1.54 +/- 0.50 mg/kg of body weight [range: 0.77-2.93]. The mean dose of AZA was 1.64 +/- 0.59 mg/kg of body weight [range: 0.47-2.97]. The maximum tolerable doses calculated for CYC and AZA were 1.25 mg/kg and 1.30 mg/kg of body weight respectively. The maximum tolerable dose for CYC and AZA among males could not be calculated, because of insufficient number of patients who developed neutropenia and thrombocytopenia. The maximum tolerable doses for CYC and AZA among females were 1.34 mg/kg and 1.03 mg/kg of body weight respectively. Also we found out that AZA was relatively more likely to cause neutropenia and thrombocytopenia [p = 0.07]

Conclusion: We thereby recommend that CYC should be initiated at a dose no more than 1 mg/kg of body weight and AZA at an initial dose of 0.75-1.0 mg/kg of body weight. The dose may be adjusted later on the basis of clinical response and laboratory reports