• Comparison of Pharmaceutical Quality and Product Performance of Albuterol Inhalers Available in the US and Those Obtained in Mexico for a Fraction of US Cost

      Myrdal, Paul; Karlage, Kelly; Nocella, Meira; Kilber, Emily; Witmer, Brittney; Myrdal, Paul; Karlage, Kelly; College of Pharmacy, The University of Arizona (The University of Arizona., 2015)
      Objectives: American residents travel to Mexico to purchase medications, like albuterol inhalers, for 1/3 to 1/5 of the US price without prescription requirements. A previous bioequivalence study found clinical differences (P less than 0.05) between Ventolin and Assal, two Mexican manufactured albuterol inhaler brands. What other differences are there among such inhalers when we test more brands and analyze pharmaceutical qualities like respirable mass? This study seeks to provide some reasonable expectations for a medical tourist of Mexico who purchases albuterol metered dose inhalers (MDIs) by comparing the product performance of some of the brands available to the consumers in Mexico. Methods: This study examined the performance of albuterol MDIs obtained from pharmacies in Nogales, Mexico. At least two units were purchased for each of the following brands: Xeneric-S, Victory, Ventolin (GlaxoSmithKline), Assal, and Sacrusyt. At least two lot numbers of each brand were included, with the exception of Sacrusyt, for which a second lot was unavailable at the purchase times. Sample MDIs were compared to US-purchased albuterol inhalers, Proventil and Ventolin. Total dose and respirable mass were determined for each MDI. These parameters were measured by actuating each inhaler into a USP throat, coupled to a cascade impactor, which separates drug particles based on aerodynamic particle size. Particles with an aerodynamic diameter larger than 4.7 micrometers are considered non-respirable, while particles less than 4.7 micrometers are considered respirable and the total of respirable and non-respirable particles is the respirable mass. The total dose delivered is determined by calculating the amount of drug that deposits onto the throat and the impactor. Quantification of albuterol was determined by high performance liquid chromatography (HPLC). In brief, the HPLC assay utilized an Apollo C18 column with a mobile phase of 1 percent phosphoric acid:methanol (77:23) at a flow rate of 0.75mL/min; UV detection was at 225 nm. Results: Every inhaler was sold in a Spanish-labeled box containing a single page instruction insert and every inhaler label had a visible lot number, expiration date, and noted a 100 microgram dose. Listed manufacturing locations included China, Mexico, India, and Spain. All of the MDIs were purchased for about $3 to $5 each except for non-US Ventolin ($10-$20 each). The measurements of total dose and respirable mass among the five Mexican purchased brands of inhalers varied widely. The MDIs’ average total doses ranged from 57 to 75 micrograms per actuation, while the average total dose of the US purchased MDIs was 79 to 82 micrograms. The respirable mass of the non-US MDIs was more similar. Among the study MDIs, respirable mass ranged from 28 to 41 micrograms, which compares to 38 to 42 micrograms for the two US branded albuterol inhalers. To further investigate the variability among the study MDIs, student t-tests were performed to compare the mean respirable mass for each brand to that of the other four brands. All comparisons were significantly different (p less than 0.05) except for two (Sacrusyt vs Assal, p equals 0.89; Xeneric vs Ventolin, p equals 0.98). Conclusions: Since significant pharmaceutical variability was found among the albuterol MDIs evaluated in this study, clinicians and patients should be conscious of possible differences in quality, therapeutic efficacy, and safety for albuterol MDIs obtained in Mexico. Sample MDIs compared to each other were statistically different in total dose and respirable mass. Thus a patient who has used US MDIs before can’t necessarily expect to get the same dose from non-US brands.
    • Stability of Tetracycline Hydrochloride in Miracle Mouthwash Formulations Containing Diphenhydramine and Dexamethasone Elixir

      Myrdal, Paul; Karlage, Kelly; Fazel, Mahdieh; Goodlet, Kellie; Myrdal, Paul; Karlage, Kelly; College of Pharmacy, The University of Arizona (The University of Arizona., 2015)
      Objectives: To assess the solubility and stability of tetracycline in compounded miracle mouthwash solutions over time, and at different temperatures (room temperature versus refrigerated) and pH (unaltered versus pH 7). Methods: Miracle mouthwash (MMW) solutions were compounded using tetracycline HCl capsules and 1:1 pseudo-dexamethasone elixir and diphenhydramine. High-performance liquid chromatography (HPLC) was used to measure the tetracycline concentrations in the MMW samples tested. Data on tetracycline crystal composition over time were also collected using powder x-ray diffraction, differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA). Results: For the tetracycline MMW solutions stored at room temperature, only 16% of the original tetracycline remained in solution after 24 hours, stabilizing at 65-81 mcg/mL on day 5 then decreasing further down to 45 mcg/mL by day 15. Similar results were obtained for the refrigerated tetracycline MMW solution (11% of original concentration after 5 days, with a decrease from 31-54 mcg/mL on day 5 to 22 mcg/mL on day 15). Tetracycline concentrations appeared to undergo a steeper decline in MMW solutions of pH 7 than in unadjusted MMW solutions (pH 4.68). All MMW samples exhibited a conversion from tetracycline HCl to tetracycline hexahydrate. Conclusions: Tetracycline solubility decreases rapidity in MMW within 24 hours of compounding regardless of temperature. MMW solutions at pH 7 may have further reduced solubility. Stability decreases at a stable rate from tetracycline HCl to tetracycline hexahydrate.