Pharmacokinetics, bioavailability, & bioequivalence Original research| Volume 34, ISSUE 11, P2221-2229, November 2012

Stability of an Alternative Extemporaneous Captopril Fast-Dispersing Tablet Formulation Versus an Extemporaneous Oral Liquid Formulation



      Administration of medications to pediatric patients is challenging because many drugs are not commercially available in appropriate dosage formulations and/or strengths. Consequently, these drugs are prepared extemporaneously as oral liquid (OL) formulations using marketed tablets or capsules. In many cases, the stability of these extemporaneous preparations, which may affect their tolerability, has not been documented. An alternative extemporaneous solid formulation, such as a fast-dispersing tablet (FDT), may offer enhanced stability as well as dosing flexibility because it may be administered as an orodispersible tablet or as a reconstituted suspension/solution. Although FDTs are available increasingly as patient-friendly oral dosage formulations, and their simple method of manufacture can be applied to extemporaneous formulations, such applications have not been explored to date.


      The use of extemporaneous captopril OL formulations in hospitals in Ireland was surveyed, and the stability of the most commonly used captopril formulation (reference) was investigated and compared with that of a newly available extemporaneous FDT formulation.


      The survey was carried out in 120 hospitals in the Republic of Ireland. The 56-day stability of the most commonly used formulation was compared with that of a newly available extemporaneous captopril FDT preparation. The captopril content of the formulations was measured by high-performance liquid chromatography analysis. Formulations were also monitored for changes in appearance, including color; odor; and pH (OLs only).


      The survey showed that extemporaneously prepared captopril OLs were extensively used, particularly in specialist children's hospitals. The most commonly used preparation was a xanthan gum–based oral suspension. Analysis of these OL preparations showed the OLs to have been stable up to day 7, but that the captopril concentration decreased to 72% to 84% at day 14 and to 59% to 68% at day 56; this decrease was accompanied by a pungent odor suggestive of captopril oxidation. In contrast, FDT formulations demonstrated greater stability, with 96% of captopril present at day 56.


      The results of this study support only a 7-day stability for the currently dispensed captopril OL in hospitals in Ireland. In contrast, a stability of at least 56 days was shown with the FDTs. The FDTs may represent an alternative and convenient oral solid extemporaneous preparation of captopril and, potentially, other extemporaneous pediatric medications.

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        • Aulton M.E.
        Aulton's pharmaceutics, the design and manufacture of medicines.
        Recherche. 2007; 67: 02
        • Liu J.
        • Chan S.
        • Ho P.
        Effects of sucrose, citric buffer and glucose oxidase on the stability of captopril in liquid formulations.
        J Clin Pharm Ther. 1999; 24: 145-150
        • Glass B.D.
        • Haywood A.
        Stability considerations in liquid dosage forms extemporaneously prepared from commercially available products.
        J Pharm Sci. 2006; 9: 398-426
        • Winckler S.
        Extemporaneous compounding: a return to regulatory limbo?.
        J Pain Palliat Care Pharmacother. 2002; 16: 71-78
        • Flynn J.T.D.S.R.
        • Daniels S.R.
        Pharmacologic treatment of hypertension in children and adolescents.
        J Pediatr. 2006; 149: 746-754
        • Helin-Tanninen M.
        • Naaranlahti T.
        • Kontra K.
        • Savolainen K.
        Nifedipine capsules may provide a viable alternative to oral powders for paediatric patients.
        J Clin Pharm Ther. 2007; 32: 49-55
        • British National Formulary
        BMJ Group and RSP Publishing.
        in: 2009: 100-101 (57)
        • Mulla H.
        • Hussain N.
        • Tanna S.
        • et al.
        Assessment of liquid captopril formulations used in children.
        Arch Dis Child. 2011; 96: 293-296
        • Mulla H.
        • Tofeig M.
        • Bu'Lock F.
        • et al.
        Variations in captopril formulations used to treat children with heart failure: a survey in the United kingdom.
        Arch Dis Child. 2007; 92: 409-411
        • Nahata M.C.
        • Allen Jr, L.V.
        Extemporaneous drug formulations.
        Clin Ther. 2008; 30: 2112-2119
        • Nahata M.C.
        Lack of pediatric drug formulations.
        Pediatrics. 1999; 104: 607-609
        • Mukattash T.
        • Hawwa A.F.
        • Trew K.
        • et al.
        Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials.
        Eur J Clin Pharmacol. 2011; 67: 449-461
        • Kadin H.
        in: Florey K. Analytical Profiles of Drug Substances. Academic Press, London, UK1982: 79-137
        • Anaizi N.
        • Swenson C.
        Instability of aqueous captopril solutions.
        Am J Health Syst Pharm. 1993; 50: 486-488
        • Nahata M.C.
        • Morosco R.S.
        • Hipple T.F.
        Stability of captopril in three liquid dosage forms.
        Am J Health Syst Pharm. 1994; 51: 95-96
        • Pereira C.
        • Tam Y.
        Stability of captopril in tap water.
        Am J Health Syst Pharm. 1992; 49: 612-615
      1. (Accessed October 10, 2012)
        • Lowey A.
        • Jackson M.
        How to ensure the quality and safety of unlicensed oral medicines.
        Pharm J. 2008; 281: 240
        • Schlatter J.
        • Sola A.
        • Saulnier J.
        Stability of an oral solution of captopril 1 mg/ml [in French].
        Journal de Pharmacie Clinique. 1997; 16: 125-128
        • Nahata M.C.
        • Morosco R.S.
        • Hipple T.F.
        Stability of captopril in liquid containing ascorbic acid or sodium ascorbate.
        Am J Health Syst Pharm. 1994; 51: 1707-1708
        • Nahata M.C.
        • Morosco R.S.
        • Hipple T.F.
        Stability of enalapril maleate in three extemporaneously prepared oral liquids.
        Am J Health Syst Pharm. 1998; 55: 1155-1157
        • Berger-Gryllaki M.
        • Podilsky G.
        • Gloor S.
        • et al.
        The development of a stable oral solution of captopril for paediatric patients.
        EJHP Sci. 2007; 1781: 20
        • Giam J.A.
        • McLachlan A.J.
        Extemporaneous product use in paediatric patients: a systematic review.
        Int J Pharm Pract. 2008; 16: 3-10
        • Pabari R.M.
        • Ramtoola Z.
        Application of face centered central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets.
        Int J Pharm. 2012; 430: 18-25
      2. Ramtoola Z, Pabari R, Kelly J. A Method of Producing Fast Dissolving Tablets. WO patent no. WO/2008/120,181.

      3. British Pharmacopoeia 2009.
        in: The British Pharmacopoeia Convention. British Pharmacopoeia, London, UK2009
      4. Xanthan Gum.
        (Accessed October 10, 2012)
        • Reiffel J.A.
        Formulation substitution: a frequently overlooked variable in cardiovascular drug management.
        Prog Cardiovasc Dis. 2004; 47: 3-10
        • McElnay J.
        • Al-Furaih T.
        • Hughes C.
        • et al.
        The effect of pH on the buccal and sublingual absorption of captopril.
        Eur J Clin Pharmacol. 1995; 48: 373-379