Stability of sotalol hydrochloride in extemporaneously prepared oral suspension formulations.

The physical, chemical, and microbial stabilities of extemporaneously compounded oral liquid formulations of sotalol hydrochloride were studied. Sotalol hydrochloride oral liquid suspensions (5mg/mL) were prepared from commercially available tablets (Betapace) in a 1:1 mixture of Ora-Plus: Ora-Sweet, a 1:1 mixture of Ora-Plus:Ora-Sweet SF, and a 1:2.4 mixture of simple syrup:methylcellulose vehicle. Six batches of each formulation were prepared; three were stored at refrigerated temperature (2 deg to 8 deg C) and three at room temperature (20 deg to 25 deg C). Samples were collected from each batch weekly for 6 weeks, and again at 12 weeks. Samples were analyzed by means of a high-performance liquid chromatographic method, and the concentrations obtained were compared to the theoretical time zero value. Samples were examined for pH, odor, color, and consistency changes. The suspensions also were evaluated for their microbial stability. Sotalol hydrochloride oral liquid suspensions (5mg/mL) were chemically stable for 12 weeks regardless of storage conditions (room temperature or refrigerated). Bacterial growth was not supported by any of the formulations. Suspensions stored at refrigerated temperature retained better physical quality (e.g., odor, color, and consistency) than suspensions stored at room temperature. Overall, this study demonstrates that oral formulations of sotalol hydrochloride can be readily prepared with commercially available vehicles. The method of preparation is relatively simple, the materials are relatively inexpensive, and the products have a shelf-life of at least 12 weeks.

Oral and subcutaneous absorption of insulin poly(isobutylcyanoacrylate) nanoparticles.

Dispersions of insulin poly(isobutylcyanoacrylate) nanoparticles were obtained by anionic in situ polymerization using aqueous pluronic acid solution. Results showed a decrease in particle size diameter by increasing the pluronic acid concentration. Nanoparticles prepared in the presence of 2.5% pluronic acid resulted in particles of 85 nm average diameter and 59% intra-particular insulin load without the use of the oily core [Damge, C., Michel, M., Aprahamian, M., Couveur, P., 1988. New approach for oral administration with polycyanoacrylate nanocapsules as drug carrier. Diabetes 37, 246-251]. In vivo testing was performed on streptozocin induced diabetic rats. The subcutaneous injection of insulin nanoparticles was able to prolong its duration of hypoglycemic effect from 6 to 72 h. Effective oral absorption of the entrapped insulin was significantly better (p<0.01) when compared with non-encapsulated insulin or the control experiments.

A novel HPLC assay for pentamidine: comparative effects of creatinine and inulin on GFR estimation and pentamidine renal excretion in the isolated perfused rat kidney.

PURPOSE: 1. To develop and validate an analytical method for pentamidine (PTM) by reversed-phase HPLC. 2. To compare the effects of creatinine and inulin on PTM excretion in the isolated perfused rat kidney. METHODS: The HPLC method utilized a base deactivated, 5 micro, C18 column and a mobile phase containing acetonitrile (24%) and 0.025 M monobasic phosphate buffer, pH 3.2 (76%). Mobile phase flow rate and UV detection wavelength were 1 mL/min and 270 nm, respectively. Sulfadiazine (SDZ) was used as the internal standard. The method was used to measure pentamidine in perfusate and urine samples generated from studies with the isolated perfused rat kidney (IPK) model. Perfusion experiments were conducted in the presence of two different GFR markers: creatinine and inulin (PTM dose 800 micro g). Both creatinine and inulin were assayed using colorimetric methods. RESULTS: The HPLC assay is rapid, sensitive and reproducible. The method was validated over two standard concentration ranges: 0.1 to 1 micro g/mL, and 1 to 10 micro g/mL. In control (drug-naïve) IPK perfusions, creatinine clearance was approximately 15% greater than inulin clearance (0.80+/- 0.21 mL/min vs. 0.69+/-0.17 mL/min, p > 0.05). In the presence of PTM, however, creatinine clearance was reduced to 0.56+/-0.27 (p < 0.05 compared to control). Inulin clearance was not altered by PTM administration (0.76+/-0.26 mL/min). Cumulative urinary excretion of PTM (% dose) was 3.0+/-0.47% and 9.6+/-4.2% in the presence of creatinine and inulin, respectively. PTM clearance was significantly reduced (0.06+/-0.01 mL/min vs. 0.13+/-0.01 mL/min, p < 0.05) and % kidney accumulation significantly enhanced (66+/-4.7% vs. 37+/-9.7%, p < 0.05) by creatinine. CONCLUSIONS: Creatinine overestimated GFR in the IPK. The altered renal excretion of PTM by creatinine is consistent with inhibition of PTM tubular secretion. Because of increased kidney accumulation, detrimental effects of PTM on renal function were observed. Based on these findings, creatinine should be used cautiously as an indicator of GFR in IPK experimentation.