Eyeworld

EW NEWS & OPINION October 2015 23 by Larry Patterson, MD From manufacture to distribu- tion, these measures are consistently monitored whenever possible to ensure the product maintains its future integrity by remaining in optimal storage conditions. Without these measures, it is possible that any sort of temperature fluctuation may cause phenylephrine hydro- chloride ophthalmic solution to degrade more rapidly, substantively impacting the structural integrity and efficacy of the solution. Conse- quently, the next time a patient is not responding well to a medication, it may be beneficial to consider the possibility that the problem might be the efficacy of drops, not just patient-related factors. EW References 1. Akers M. Sterile Drug Products: Formulation, Packaging, Manufacturing and Quality, pg. 100. 2. David BT, Beringer P. Eds. Remington: The Science and Practice of Pharmacy, pg. 1030. 3. US 20090047343 A1 4. Douša M, Gibala P, Havlícek J, et al. Drug-excipient compatibility testing – Identi- fication and characterization of degradation products of phenylephrine in several phar- maceutical formulations against the common cold. J Pharm Biomed Anal. 2011;55(5):949– 956. 5. Luduena FP, Snyder AL, Lands AM. Effect of ultra-violet irradiation of phenylephrine. J If degradation and decreased potency have transpired causing a product to become less active, this could lead physicians to use more of the drug in order to achieve the de- sired result. This should be avoided as overuse of any product can incite adverse events. In the case of phen- ylephrine ophthalmic solution, with 94 million eye exams performed annually in the United States, 8 most of which require dilation, this could create a great potential for over dosage. Checks and balances system within the supply chain With phenylephrine's tendency to degrade and oxidize under higher temperatures, maintaining refriger- ated storage conditions from factory to office is essential. Despite the im- portance, attention to maintaining optimal temperatures is not typical of most supply chain procedures. In the case of phenylephrine hydrochloride from Paragon BioTeck (Portland, Ore.), it takes approxi- mately 12 to 18 weeks from the start of manufacture to the time it enters into the supply chain. While several studies have shown that phenyleph- rine is still efficacious even when left at room temperature for short periods of time, 9,10,11 in supply chain, drugs can often be stored or trans- ported at much higher temperatures, a definite cause for concern. A bottle left on the counter of a physician's office overnight will most likely not degrade to the point that potency is affected. Paragon BioTeck has instituted a system of checks and balances throughout the entire process. Environmentally controlled ship- ping and storage conditions are maintained to preserve formulation integrity and keep the product at peak potency. During the shipping process, optimal storage conditions are monitored through the truck's infor- mation and temperature readouts. Additionally, Paragon BioTeck utiliz- es other redundancies to ensure the product stays within those storage conditions. What you see isn't always what you get T he chain of supply a drug traverses from manufac- turer to the physician's office is a crucial but often overlooked process. Many products require specialized storage conditions, and while these require- ments are generally met within the office setting, there is rarely any guarantee that these are being maintained while the product is in transit. For some products such as phenylephrine hydrochloride ophthalmic solution, transit con- ditions are especially critical as this product can oxidize and degrade when exposed to light and higher temperatures. 1,2,3 Maintaining product integrity For many products such as phen- ylephrine, minimizing exposure to higher temperature conditions aids in optimizing product integrity and efficacy. Even in specialized pack- aging some physical and chemical degradation can occur, which may result in decreased potency and effectiveness. 4,5,6,7 While certain forms of degradation may provide visual warning signs that a product may be compromised, other forms of degradation can only be detected through special analytical testing. For phenylephrine, oxidation is one form of degradation that may pro- vide us with warning signs that are helpful in visually detecting degra- dation. Oxidation is known to some- times cause the clear phenylephrine solution to turn yellowish or brown in color. In contrast, there are other forms of degradation of phenyl- ephrine that may not be observed visually in the absence of specialized analytical testing. Racemization is one such form of degradation. This degradation causes the biologically active part of the drug's molecule to slowly morph to the less biologically active side of the molecule. This is just one example of a form of degra- dation that may occur where there is no visual warning sign provided. Impact of optimal supply chain practices Pharm Pharmacol. 1963;15:538–543. 6. Al Taji RA, Stanford JB, Sugden JK. Some aspects of the photolysis of aqueous solutions of phenylephrine hydrochloride. Pharm Acta Helv. 1982;57:56–60. 7. El-Shibini HAM, Daabis NA, Motawi MM. The Stability of Phenylephrine: Part I. The Rate of Degradation of the Amino Group. 19 (1969) pgs. 676–678. 8. AOA Excel and Jobson Medical Informa- tion. Seeing the world better: the state of the optometric profession: 2013, pg. 4. 9. Kiser TH, Oldland AR, Fish DN. Stability of phenylephrine hydrochloride injection in poly- propylene syringes. Am J Health Syst Pharm. 2007;64(10):1092–5. 10. Jansen JJ, Oldland AR, Kiser TH. Evalu- ation of phenylephrine stability in polyvinyl chloride bags. Hosp Pharm. 2014;49(5): 455–7. 11. Dreno C, Gicquel T, Harry M, Tribut O, Aub- in F, Brandhonneur N, Dollo G. Formulation and stability study of a pediatric 2% phenylephrine hydrochloride eye drop solution. Ann Pharm Fr. 2015;73(1):31–6. Editors' note: Dr. Patterson is the medi- cal director of Eye Centers of Tennessee and the Cataract and Laser Center. He has financial interests with Paragon Bioteck. Contact information Patterson: larryp@ecotn.com " Many products require specialized storage conditions, and while these requirements are generally met within the office setting, there is rarely any guarantee that these are being maintained while the product is in transit. "

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