Mary K. Stamatakis

Influence of pH on the dissolution of folic acid supplements.

The vitamin folic acid has received considerable attention because of its role in decreasing the risk of neural tube birth defects, and its potential role in reducing the risks of cardiovascular and psychiatric diseases. A significant concern is the quality of commercially available folic acid products. We evaluated the pharmaceutical performance of 15 currently available folic acid products in terms of meeting the USP standards for disintegration and dissolution, and showed that there has been significant improvement in the past decade in the quality of these products. However, at least one product failed to meet the requirement of each test performed. Since folic acid absorption is maximal at the proximal jejunum, dissolution was further evaluated in simulated gastric fluid. All the products failed to release more than 75% of the active ingredient in 60min. While some excipient-related factors were preliminarily considered, it was ultimately proposed that the failure may be related to the pH-dependency of the solubility of folic acid, a premise supported by faster dissolution of laboratory prepared buffered folic acid tablets. The more limited solubility of folic acid in acidic medium should be taken into consideration in the required dissolution testing methods, as well as in product formulation to optimize release.

Interaction between Quinupristin/Dalfopristin and Cyclosporine

OBJECTIVE: To describe a case of a drug interaction between cyclosporine and quinupristin/dalfopristin (QND). CASE SUMMARY: A patient who had undergone a kidney transplant and was receiving chronic cyclosporine therapy was treated with the investigational streptogramin antibiotic QND. Baseline trough cyclosporine concentrations ranged from 80 to 105 ng/mL. Two and 3 days after initiation of QND therapy, trough cyclosporine concentrations increased to 261 and 291 ng/mL, respectively. Following discontinuation of QND, the cyclosporine blood concentration decreased and the dosage was subsequently increased to the previous regimen. DISCUSSION: A patients cyclosporine blood concentration tripled 3 days after initiating therapy with QND. A one-third reduction in the cyclosporine dosage was required. QND was the most likely cause for the change in cyclosporine blood concentrations, probably due to inhibition of cyclosporine metabolism. This represents the first published case of an interaction between cyclosporine and QND. CONCLUSIONS: Frequent monitoring of cyclosporine concentrations with attention to the need for dosage modification is recommended when initiating or discontinuing QND therapy.

Influence of pH on In Vitro Disintegration of Phosphate Binders

Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a products performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.

Survival after metformin-associated lactic acidosis in peritoneal dialysis-dependent renal failure

caused by immune complex formation, by paraproteins, with subsequent complement activation.” This mechanism is not likely in our patient because of the absence of cryoglobulins, the negative Clq binding assay, and the absence of immune complexes in the biopsy. Antibody activity against neuronal tissue, like MAG antibodies, as a possible mechanism of neuropathy7 has also been excluded in our patient. We conclude that the vasculitis in this patient is not related to the multiple myeloma but to the PAN. The presence of cANCA and antibodies against PR3 further support this diagnosis.” The role of autoantibodies in the pathogenesis of vasculitis, however, remains unknown. M etformin (MET), a dimethylbiguanide antihyperglycemic agent, has shown promise for its efficacy in improving glycemic control while causing adipose tissue and weight loss in obese non-insulindependent diabetic (NIDDM) patients.‘-” Unlike its predecessor, phenformin, which was removed from the US market in the 197Os, MET has less propensity for causing lactic acidosis, although in certain subgroups of patients, including those with renal insufficiency in whom MET elimination is decreased, the risk of lactic acidosis remains a serious concern.“,” Well-documented cases of metformin-associated lactic acidosis (MALA) in patients with chronic renal failure are few,i,8 and to our knowledge, no case of MALA has been reported in a patient already on peritoneal dialysis (PD).“,‘” We describe MALA in a renal failure patient on PD who was inadvertantly given MET and survived this life-threatening complication.

Student and Faculty Perceptions of Lecture Recording in a Doctor of Pharmacy Curriculum

Objective. To describe students’ and faculty members’ perceptions of the impact of lecture recording in a doctor of pharmacy (PharmD) curriculum. Methods. Second- and third-year pharmacy students and faculty members completed an anonymous survey instrument regarding their perceptions of lecture recording with 2 classroom lecture capture software programs, Camtasia Studio and Wimba Classroom. Results. Most students (82%) responded that Camtasia was very helpful and almost half (49%) responded that Wimba Classroom was helpful (p<0.001). Forty-six percent of the students reported being more likely to miss a class that was recorded; however, few students (10%) reported using recordings as a substitute for attending class. The most common concern of faculty members was decreased student attendance (27%). Conclusion. Pharmacy students consider lecture recordings beneficial, and they use the recordings primarily to review the lecture. While faculty members reported concerns with decreased attendance, few students reported using recordings as an alternative to class attendance.

Disintegration performance of renal multivitamin supplements.

OBJECTIVE Vitamins have traditionally been regulated as dietary supplements and have not been required to meet the same rigorous product quality performance standards as drug products. Impaired product performance, such as failure to disintegrate and/or dissolve in the gastrointestinal tract, could limit the absorption of vitamins. Furthermore, patients with renal disease have been reported to experience a wide range in gastrointestinal pH, which could influence a products performance. The purpose of this study was to determine the effect of pH on the in vitro disintegration of renal multivitamin supplements. DESIGN Products were studied using the United States Pharmacopeial Convention standard disintegration apparatus. Products were tested in simulated gastric fluid, neutral fluid, and intestinal fluid. Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within compendial limits. RESULTS Of 11 products tested, 4 products failed the disintegration study test in all pH conditions. Sixty-four percent of the products showed statistically significant differences in disintegration time (DT) based on pH. As pH increased, time to disintegration increased. CONCLUSION The DT of commercially available renal multivitamin supplements was highly variable. Poorest product performance was shown in simulated intestinal fluid. The pH significantly affected in vitro disintegration in greater than half the products tested. How this affects dissolution and in vivo performance has yet to be studied.