Physicochemical Stability of an Oral Suspension of Trimethoprim 20 mg/mL in Combination with Sulfadiazine 200 mg/mL in PCCA Base SuspendIt.

Trimethoprim is a diaminopyrimidine antibacterial agent that, like sulfonamides, inhibits bacterial folic acid synthesis, but at a different stage in the metabolic pathway. It has a similar spectrum of activity to the sulfonamides and is given by mouth or by injection, either alone or in conjunction with a sulfonamide, such as sulfadiazine. Sulfadiazine is a bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. The combination of the two drugs produces a synergistic effect against both Gram-positive and Gram-negative aerobic bacteria, by inhibiting enzymes in the folic acid pathways, which in turn inhibits bacterial thymidine synthesis. There are no published studies of the stability of the combination of trimethoprim and sulfadiazine in a liquid dosage form. An extemporaneously compounded suspension from pure drug powders or commercial tablets would provide an alternative option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of trimethoprim combined with sulfadiazine in PCCA base SuspendIt. PCCA base SuspendIt is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating high-performance liquid chromatographic assay for the simultaneous determination of trimethoprim and sulfadiazine in SuspendIt was developed and validated. This assay was used to determine the chemical stability of both drugs in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, 40°C), and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 0, 7, 14, 30, 45, 60, 91, 120, and 182 days at each designated temperature. Physical data such as pH, viscosity, appearance, and average particle size were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at room temperature and in the refrigerator. The pH values also did not change significantly. There was some variability in viscosity and average particle size. This study demonstrates that trimethoprim and sulfadiazine are physically and chemically stable in combination in SuspendIt for 182 days at room temperature and in the refrigerator, thus providing a viable, compounded alternative for both drugs in a liquid dosage form, with an extended beyond-use-date to meet patient needs.

Stability of Spironolactone Oral Suspension in PCCA Base, SuspendIt.

Spironolactone (Aldactone) is a potassium-sparing diuretic used to treat hypertension and heart failure and may also be used to treat edema resulting from kidney disease, low potassium levels, or excess aldosterone. No commercial liquid dosage form of spironolactone exists. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide an alternative option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of spironolactone in the PCCA base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating highperformance liquid chromatographic assay for the determination of spironolactone in PCCA base SuspendIt was developed and validated. This assay was used to determine the chemical stability of the drug in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, 40°C) and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 0, 7, 14, 29, 46, 60, 90, 120, and 180 days at each designated temperature. Physical data such as pH, viscosity, and appearance were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at all three temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that spironolactone is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for spironolactone in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Stability of Clindamycin Hydrochloride in PCCA Base SuspendIt.

Clindamycin is an effective antibiotic in the treatment of infections caused by certain gram-positive and gram-negative anaerobic microorganisms. While manufactured forms of the drug for pediatric use are available, there are instances when a compounded liquid dosage form is essential to meet unique patient needs. The purpose of this study was to determine the chemical stability of clindamycin hydrochloride in the PCCA base SuspendIt, a sugar-free, paraben- free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating high-performance liquid chromatographic assay for the determination of clindamycin hydrochloride in SuspendIt was developed and validated. This assay was used to determine the chemical stability of the drug in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, and 40°C), and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 7, 14, 30, 45, 60, 91, 120, and 182 days at each designated temperature. Physical data such as pH, viscosity, and appearance were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at all three temperatures studied, barring isolated experimental errors. Viscosity and pH values also did not change significantly. Some variations in viscosity were attributed to the thixotropic nature of the vehicle. This study demonstrates that clindamycin hydrochloride is physically and chemically stable in SuspendIt for 182 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for clindamycin hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Assessment of bone mineral status in children with Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ß, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone mineralization in children with MFS. Using dual-energy X-ray absorptiometry (DXA), we evaluated bone mineralization in 20 children with MFS unselected for bone problems. z-Scores were calculated based on age, gender, height, and ethnicity matched controls. Mean whole body bone mineral content (BMC) z-score was 0.26±1.42 (P=0.41). Mean bone mineral density (BMD) z-score for whole body was -0.34±1.4 (P=0.29) and lumbar spine was reduced at -0.55±1.34 (P=0.017). On further adjusting for stature, which is usually higher in MFS, mean BMC z-score was reduced at -0.677±1.37 (P=0.04), mean BMD z-score for whole body was -0.82±1.55 (P=0.002) and for lumbar spine was -0.83±1.32 (P=0.001). An increased risk of osteoporosis in MFS is controversial. DXA has limitations in large skeletons because it tends to overestimate BMD and BMC. By adjusting results for height, age, gender, and ethnicity, we found that MFS patients have significantly lower BMC and BMD in whole body and lumbar spine. Evaluation of diet, exercise, vitamin D status, and bone turnover markers will help gain insight into pathogenesis of the reduced bone mass. Further, larger longitudinal studies are required to evaluate the natural history, incidence of fractures, and effects of pharmacological therapy.

Generalized metabolic bone disease in Neurofibromatosis type I.

Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1) but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical and pathological level the bone involvement in NF1 patients. Using dual energy X-ray absorptiometry (DXA) we analyzed bone status in 73 unselected NF1 subjects, 26 males and 47 females, mainly children and adolescents (mean age: 16.6 years). In a subgroup of subjects with low bone mass, we measured indices of calcium-phosphate metabolism, bone turnover, and bone density before and after vitamin D and calcium treatment. We found statistically significant and generalized reduction in bone mass with the mean lumbar bone mineral density (BMD) z-score being -1.38+/-1.05 (CI 95% -1.62 to -1.13), and whole body bone mineral content (BMC) z-score -0.61+/-1.19 (CI 95% -0.94 to -0.29), both significantly reduced compared to normal controls (p<.001). PTH was moderately elevated and after 4 months of supplemental therapy with calcium and vitamin D, it decreased to the normal range. However, BMD z-scores did not significantly improve after 2 years of follow-up. Histological analysis of bone samples from NF1 patients revealed substantial alteration of bone microarchitecture due mainly to reduced trabecular bone. Our observations are consistent with a generalized bone metabolic defect due to loss of the function of neurofibromin. Early identification of patients with osteoporosis may permit more timely and aggressive treatments to prevent the likely substantial morbidity associated with increased fracture risk later in life.