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Nuclear medicine techniques in the evaluation of pharmaceutical formulations

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Abstract

Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the Gl tract, the depth of penetration of a nebulised solution into the lung, or the residence time of a drug on the cornea. Using the gamma camera to image the in vivo distribution of pharmaceutical formulations radiolabelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers.

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References

  1. Wilson CG, Hardy JG, Frier M and Davis SS. Eds Radionuclide imaging in drug research. Croom Helm, London 1982.

    Google Scholar 

  2. Wilson CG and Perkins AC. Gamma Scintigraphy and the study of drug deposition. In: Advances in Pharmaceutical Sciences. Eds. Ganderton D and Jones T. Academic Press, London, 1992.

    Google Scholar 

  3. Davis SS, Hardy JG, Newman SP, Wilding IR. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms. Eur J Nucl Med 1992;19:971–986.

    Google Scholar 

  4. Burns HD, Gibson RE, Dannals and Siegl PKS. Eds. Nuclear Imaging in drug discovery, development and approval. 1993, Birkhauser, Boston.

    Google Scholar 

  5. Meseguer G, Buri P, Gurny R. Application of medical imaging to pharmaceutical research: The example of gamma scintigraphy: I. Technological aspects. European Journal of Pharmaceutics and Biopharmaceutics, 1994;40:111–121.

    Google Scholar 

  6. Meseguer G, Gurny R, Buri P. In vivo evaluation of dosage forms: Application of gamma scintigraphy to non-enteral routes of administration. Journal of Drug Targeting. 1994;2:269–288.

    Google Scholar 

Oral drug delivery

  1. Tolin R D, Malmud L S, Reilley J, Fisher R S. Oesophageal scintigraphy to quantitate oesophageal transit (Quantitation of oesophageal transit). Gastroenterology 1979;76:1402–1409.

    Google Scholar 

  2. Davis SS, Daly PB, Frier M, Hardy JG, Kennerley JW, Wilson CG. The design and evaluation of sustained release formulations for oral and buccal administration. Adv Pharmacother 1981;1:17–25.

    Google Scholar 

  3. Daly PB, Davis SS, Frier M, Hardy JG, Kennerly JW, Wilson CG. Scintigraphic assessment of the in-vivo dissolution rate of a sustained release tablet. Int J Pharm 1982;10:17–24.

    Google Scholar 

  4. Davis SS, Hardy JG, Taylor MJ, Stockwell A, Whalley DR, Wilson CG. The in-vivo evaluation of an osmotic device (Osmet) using gamma scintigraphy. J Pharm Pharmacol 1984;36:740–742.

    Google Scholar 

  5. Davis SS, Hardy JG, Taylor MJ, Stockwell A, Whalley DR, Wilson CG. The effect of food on the gastrointestinal transit of pellets and an osmotic device. Int J Pharm 1984;21:331–340.

    Google Scholar 

  6. May HA, Wilson CG, Hardy JG. Monitoring radiolabelled antacid preparations in the stomach. Int J Pharmaceutics 1984;19:169–176.

    Google Scholar 

  7. Hardy JG, Wilson CG, Wood E. Drug delivery to the proximal colon. J Pharm Pharmacol 1985; 37:874–877.

    Google Scholar 

  8. Parr AF, Beihn RM, Franz RM, Szpunar GJ, Jay M. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of 171Er labelled sustained-release tablets. Pharm Res 1987;4:486–489.

    Google Scholar 

  9. Ollerenshaw KJ, Norman S, Wilson CG and Hardy JG. Exercise and small intestinal transit. Nucl Med Commun. 1987;8:105–110.

    Google Scholar 

  10. Mundy MJ, Wilson CG, Hardy JG. The effect of eating on transit through the small intestine. Nucl Med Commun. 1989;10:45–50.

    Google Scholar 

  11. Wilson CG, Washington N, Greaves JL, Blackshaw PB, Perkins AC, Barkworth MF, Rehm KD. Effect of pretreatment with ranitidine on the transit of a sustained release theophylline preparation. Arzneimittel-Forschung Drug Research 1991; 41:1154–1159.

    Google Scholar 

  12. Coupe AJ, Davis SS, Wilding IR. Variation in gastrointestinal transit of pharmaceutical dosage forms in healthy subjects. Pharm Res 1991;8:360–364.

    Google Scholar 

  13. Davis SS, Robertson C, Wilding IR. Gastrointestinal transit of a multiparticulate tablet formulation in patients with active ulcerative colitis. Int J Pharm 1991;199–204.

  14. Roca M, Carrio I, Monés J, Mora J, Estorch M, Berná L. Labelling procedure of antacid preparations using 99mTc-prophosphate. Int J Pharmacol. 1991;69:189–192.

    Google Scholar 

  15. Monés J, Carrio I, Rocca M et al. Gastric emptying of two radiolabelled antacids. Gut 1991;32:147–150.

    Google Scholar 

  16. Coupe AJ, Davis SS, Evans DF, Wilding IR. Correlation of the gastric emptying of non-disintegrating tablets with gastrointestinal motility. Pharm Res 1991;8:1281–1285.

    Google Scholar 

  17. Course NJ, Newton JM, Short MD. Stomach outline visualization in gastrointestinal transit studies using scintigraphy. Journal of Pharmacy and Pharmacology, 1992;44:127–129.

    Google Scholar 

  18. Coupe AJ, Davis SS, Evans DF, Wilding IR. The effect of sleep on the gastrointestinal transit of pharmaceutical dosage forms. International Journal of Pharmaceutics, 1992;78:69–76.

    Google Scholar 

  19. Washington N, Moss HA, Washington C, Greaves JL, Steele RJC, Wilson CG. Non-invasive detection of gastro-oesophageal reflux using an ambulatory system. Gut, 1993;34:1482–1486.

    Google Scholar 

  20. Washington N, Wilson CG, Williams DL, Robertson C. An investigation into the effect of cimetidine pre-treatment on raft formation of an anti-reflux agent. Alimentary Pharmacology and Therapeutics 1993;7:553–559.

    Google Scholar 

  21. Clarke GM, Newton JM, Short MD. Gastrointestinal transit of pellets of differing size and density. International Journal of Pharmaceutics 1993;100:81–92.

    Google Scholar 

  22. Hardy JG, Harvey WJ, Sparrow RA, Marshall GB, Steed KP, Macarios M, Wilding IR. Localization of drug release sites from an oral sustained-release formulation of 5-ASA (Pentasa(R)) in the gastrointestinal tract using gamma scintigraphy. Journal of Clinical Pharmacology. 1993;33:712–718.

    Google Scholar 

  23. Davis SS, Wilding EA, Wilding IR. Gastrointestinal transit of a matrix tablet formulation: Comparison of canine and human data. International Journal of Pharmaceutics 1993;94:235–238.

    Google Scholar 

  24. Ashford M, Fell JT, Attwood D, Sharma H, Woodhead PJ. An in vivo investigation into the suitability of pH dependent polymers for colonic targeting. International Journal of Pharmaceutics 1993;95:193–199.

    Google Scholar 

  25. Price JMC, Davis SS, Wilding IR. Characterization of colonic transit of nondisintegrating tablets in healthy subjects. Digestive Diseases and Sciences 1993;38:1015–1021.

    Google Scholar 

  26. Coupe AJ, Davis SS, Evans DF, Wilding IR. Do pellet formulations empty from the stomach with food? International Journal of Pharmaceutics 1993;92:167–175.

    Google Scholar 

  27. Abrahamsson B, Alpstein M, Hugosson M, Jonsson UE, Sundgren M, Svenheden A, Tolli J. Absorption, gastrointestinal transit, and tablet erosion of felodipine extended-release (ER) tablets. Pharmaceutical Research 1993;10:709–714.

    Google Scholar 

  28. Ebel JP, Jay M, Beihn RM. An in vitro/in vivo correlation for the disintegration and onset of drug release from enteric-coated pellets. Pharmaceutical Research 1993;10:233–238.

    Google Scholar 

  29. Adkin DA, Davis SS, Sparrow RA, Wilding IR. Colonic transit of different sized tablets in healthy subjects. Journal of Controlled Release 1993;23:147–156.

    Google Scholar 

  30. Davies NM, Farr SJ, Kellaway IW, Taylor G, Thomas M. A comparison of the gastric retention of alginate containing tablet formulations with and without the inclusion of excipient calcium ions. International Journal of Pharmaceutics, 1994;105:97–101.

    Google Scholar 

  31. Wilding IR, Davis SS, Steed KP, Sparrow RA, Westrup J, Hempenstall JM. Gastrointestinal transit of a drug-resinate administered as an oral suspension. International Journal of Pharmaceutics 1994;101:263–268.

    Google Scholar 

  32. Parikh R, Sweetland J, Forster ER, Bedding AW, Farr SJ, Smith JTL. Ranitidine bismuth citrate and ranitidine do not affect gastric empyting of a radio-labelled liquid meal. British Journal of Clinical Pharmacology 1994;38:577–580.

    Google Scholar 

  33. Sangekar SA, Sandefer EP, Page RC, Vadino WA, Saffran M, Chaudry I, Digenis GA. Comparative scintigraphic evaluation of aromatic-azo polymers and Eudragit((R)) S-100 for colonic release in beagles. Proceedings of the Controlled Release Society 1994;21:330–331.

    Google Scholar 

  34. Wilding IR, Davis SS, Pozzi F, Furlani P, Gazzaniga A. Enteric coated timed release systems for colonic targeting. International Journal of Pharmaceutics 1994;111:99–102.

    Google Scholar 

  35. Perkins AC, Wilson CG, Blackshaw PE, Vincent RM, Dansereau RJ, Juhlin KD, Bekker PJ, Spiller RC. Impared oesophageal transit of capsule versus tablet formulations in the elderly. Gut 1994;35:1363–1367.

    Google Scholar 

  36. Olsson B, Wagner ZG, Mansson P, Ragnarsson G. A gamma scintigraphic study of the absorption of morphine from controlled-release tablets. International Journal of Pharmaceutics 1995;119:223-.

    Google Scholar 

  37. Kenyon CJ, Hooper G, Tierney D, Butler J, Devane J, Wilding IR. The effect of food on the gastrointestinal transit and systemic absorption of naproxen from a novel sustained release formulation. Journal of Controlled Release 1995;34:31–36.

    Google Scholar 

  38. Adkin DA, Davis SS, Sparrow RA, Huckle PD, Phillips AJ, Wilding IR. The effects of pharmaceutical excipients on small intestinal transit. British Journal of Clinical Pharmacology 1995;39:381–387.

    Google Scholar 

  39. Podczeck F, Newton JM, Yuen KH. The description of the gastrointestinal transit of pellets assessed by gamma scintigraphy using statistical moments. Pharmaceutical Research 1995;12;376–379.

    Google Scholar 

  40. Adkin DA, Davis SS, Sparrow RA, Huckle PD, Phillips AJ, Wilding IR. The effect of different concentrations of mannitol in solution on small intestinal transit: Implications for drug absorption. Pharmaceutical Research 1995;12:393–396.

    Google Scholar 

  41. Monés J, Carrio I, Sainz S, Berná L, Clavé P, Liszkay M, Rocca M, Vilardell F. Gastric emptying of two radiolabelled antacids with simultaneous monitoring of gastric pH. Eur J Nucl Med 1995;22:1123–1128.

    Google Scholar 

  42. Wilding IR, Davis SS, Sparrow RA, Ziemniak JA, Heald DL. Pharmacoscintigraphic evaluation of a modified release (Geomatrix(R)) diltiazem formulation. Journal of Controlled Release 1995;33:89–97.

    Google Scholar 

  43. Clarke GM, Newton JM, Short MB. Comparative gastrointestinal transit of pellet systems of varying density. International Journal of Pharmaceutics 1995;114:1–11.

    Google Scholar 

Enemas and Suppositories

  1. Hardy JG, Lee SW, Clark AG, Reynolds JR. Enema volume and spreading. Int J Pharm 1986; 31: 151–155.

    Google Scholar 

  2. Hardy JG, Feely LC, Wood E, Davis SS. The application of gamma scintigraphy for the evaluation of the relative spreading of suppository bases in rectal hard gelatin capsules. Int J Pharm 1987; 38:103–108.

    Google Scholar 

  3. Jay M, Beihn RM, Digenis GA, DeLand FH, Caldwell L, Mlodozeniec AR. Disposition of radiolabelled suppositories in humans. J Pharm Pharmacol 1985; 37:266–268.

    Google Scholar 

  4. Wilding IR, Kenyon CJ, Chauhan KS, Hooper G, Marshall S, McCracken JS, Staab HJ, Armbrecht J. Colonic spreading of a non-chlorofluorocarbon mesalazine rectal foam enema in patients with quiescent ulcerative colitis. Alimentary Pharmacology and Therapeutics, 1995;9:161–166.

    Google Scholar 

Nasal drug delivery

  1. Lee SW, Hardy JG, Wilson CG, Smelt GJC. Nasal sprays and polyps. Nucl Med Commun. 1984; 5:697–703.

    Google Scholar 

  2. Hardy JG, Lee SW and Wilson CG. Intranasal drug delivery by spray and drops. J Pharm Pharmacol 1985; 37:294–297.

    Google Scholar 

  3. Newman SP, Morén F, Clarke SW. The nasal distribution of metered dose inhalers. J Laryngol Otol 1987;101: 127–132.

    Google Scholar 

  4. Newman SP, Morén F, Clarke SW. Deposition pattern from a nasal pump spray. Rhinology 1987; 25:77–82.

    Google Scholar 

  5. Pennington AK, Ratcliffe JH, Wilson CG, Hardy JG. The influence of solution viscosity on nasal spray deposition and clearance. Int J Pharm 1988; 43: 221–224.

    Google Scholar 

Pulmonary drug delivery

  1. Newman SP, Pavia D, Morén F, Sheahan NF, Clarke SW. Deposition of pressurised aerosols in the human respiratory tract. Thorax 1981;36:52–55.

    Google Scholar 

  2. Newman SP, Morén F, Pavia D, Corrado O, Clarke SW. The effect of changes in metered volume and propellant vapour pressure on the deposition of pressurised inhalation aerosols. Int J Pharm 1982;11:337–344.

    Google Scholar 

  3. Newman SP, Killip M, Pavia D, Morén F, Clarke SW. The effect of changes in particle size on the deposition of pressurised inhalation aerosols. Int J Pharm 1984;19:333–337.

    Google Scholar 

  4. Newman SP, Millar AB, Lennard-Jones TR, Moren F, Clarke SW. Improvement of pressurised aerosol deposition with Nebhaler spacer device. Thorax 1984;39:935–941.

    Google Scholar 

  5. Newman SP, Morén F, Clarke SW. Deposition pattern of nasal sprays in man. Rhinology 1988;26:111–120.

    Google Scholar 

  6. Newman SP, Woodman G, Clarke SW. Deposition pattern of carbencillin aerosols in cystic fibrosis: effect of nebuliser system and breathing pattern. Thorax 1988;43:318–322.

    Google Scholar 

  7. Ashworth HL, Wilson CG, Sims EE, Wotton PK, Hardy JG. Delivery of propellant soluble drug from a metered dose inhaler. Thorax 1991; 46:245–247.

    Google Scholar 

  8. Newman SP, Weisz AWB, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. Thorax 1991; 46:712–716.

    Google Scholar 

  9. Colthorpe P, Farr SJ, Taylor G, Smith IJ, Wyatt D. The pharmacokinetics of pulmonary-delivered insulin: A comparison of intratracheal and aerosol administration to the rabbit. Pharmaceutical Research, 1992;9:764–768.

    Google Scholar 

  10. Hardy JG, Newman SP, Knoch M. Lung deposition from four nebulizers. Respiratory Medicine, 1993;87:461–465.

    Google Scholar 

  11. Borgstrom L, Newman S. Total and regional lung deposition of terbutaline sulphate inhaled via a pressurised MDI or via Turbuhaler(R). International Journal of Pharmaceutics, 1993;97:47–53.

    Google Scholar 

  12. Harnor KJ, Perkins AC, Wastie M, Wilson CG, Sims EE, Feely LC and Farr SJ. Effect of vapour pressure on the deposition pattern from solutions and metered dose inhalers. Int J Pharmaceutics 1993; 95:111–116.

    Google Scholar 

  13. Atkins P, Clark AR. Drug delivery to the respiratory tract and drug dosimetry. Journal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung, 1994;7:33–38.

    Google Scholar 

  14. Farr SJ, Ho KKL, Kellaway IW. A gamma scintigraphic study of tracheo-bronchial deposition and clearance of nebulized aerosols. STP Pharma Sciences, 1994;4:23–28.

    Google Scholar 

  15. Pitcairn G, Lunghetti G, Ventura P, Newman S. A comparison of the lung deposition of salbutamol inhaled from a new dry powder inhaler, at two inhaled flow rates. International Journal of Pharmaceutics 1994;102:11–18.

    Google Scholar 

  16. Farr SJ, Rowe AM, Rubsamen R, Taylor G. Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler. Thorax 1995;50:639–644.

    Google Scholar 

Ocular drug delivery

  1. Wilson CG, Olejnik O, Hardy JG. Precorneal drainage of polyvinyl alcohol solutions in the rabbit assessed by gamma scintigraphy. J Pharm Pharmacol 1983;35:451–454.

    Google Scholar 

  2. Zaki I, Fitzgerald P, Hardy JG, Wilson CG. A comparison of the effect of viscosity on the precorneal residence of solutions in man and rabbit. J Pharm Pharmacol 1986;38:463–466.

    Google Scholar 

  3. Fitzgerald P, Hadgraft J, Kreuter J, Wilson CG. A gamma scintigraphic evaluation of microparticulate ophthalmic delivery systems: liposomes and nanoparticles. In J Pharm 1987; 40:81–84.

    Google Scholar 

  4. Greaves JL, Wilson CG, Rozier A, Grove J, Plazonnet B. Scintigraphic assessment of an ophthalmic gelling vehicle in man and rabbit. Curr Eye Res. 1990; 9:415–420.

    Google Scholar 

  5. Snibson GR, Greaves JL, Soper NDW, Prydal JI, Wilson CG, Bron AJ. Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy. Eye 1990;4:594–602.

    Google Scholar 

  6. Greaves JL, Wilson CG, Galloway NR, Birmingham AT, Olejnik O. A comparison of the precorneal residence of an artificial tear preparation in patients with keratoconjunctivitis sicca and normal volunteer subjects using gamma scintigraphy. Acta Ophthalmologica 1991;69:432–436.

    Google Scholar 

  7. Greaves JL, Wilson CG, Birmingham AT. Assessment of the precorneal residence of an ophthalmic ointment in healthy subjects. Br J Pharmacol 1993; 35:188–192.

    Google Scholar 

  8. Meseguer G, Gurny R, Buri P, Rozier A, Plazonnet B. Gamma scintigraphic study of precorneal drainage and assessment of miotic response in rabbits of various ophthalmic formulations containing pilocarpine. Int J Pharm 1993;95:229–234.

    Google Scholar 

General References

  1. EEC notes for guidance: Good clinical practice for trials on medicinal products in the European Community. Pharmacology and Toxicology 1990;67:361–372.

    Google Scholar 

  2. World Health Organisation. Proposed international guidelines for biochemical research involving human subjects. 1982 Geneva: CIOMS.

    Google Scholar 

  3. International Commission on Radiological Protection. Radiological protection in biomedical research. ICRP Publication 62. 1993, Pergamon Press, Oxford.

    Google Scholar 

  4. Parr AF, Jay M, Digenis GA, Beihn RM. Radiolabelling of intact tablets by neutron activation for in vivo scintigraphic studies. J Pharm Sci 1985;74:590–591.

    Google Scholar 

  5. Parr AF, Beihn RM, Jay M. In vivo scintigraphy evaluation of enteric coated tablets using neutron activation of erbium-170. Int J Pharm 1986;32:251–256.

    Google Scholar 

  6. Parr AF, and Jay M. Radiolabelling of intact doage forms by neutron activation: effects on in vitro performance. Pharm Res 1987;4:526–528.

    Google Scholar 

  7. Awang MB, Hardy JG, Davis SS, Wilding IR, Parry SJ. Radiolabelling of pharmaceutical dosage forms by neutron activation of samarium-152. Journal of Labelled Compounds and Radiopharmaceuticals, 1993;33:941–948.

    Google Scholar 

  8. Mountford PJ. Radiation risk and ethical consent. Nucl Med Commun 1995;16:1–3.

    Google Scholar 

  9. 91/356/EEC Principles and guidelines of good manufacturing practice for medicinal products for human use 1991. O J of European Communities No L 139.

  10. Hardy JG and Perkins A C. Validity of the geometric mean correction in the quantification of whole bowel transit. Nucl Med Commun 1985;6: 217–224.

    Google Scholar 

  11. Phipps PR, Gonda I, Bailey DL, Borham P, Bautovich G, Andersen SD. Comparisons of planar and tomographic gamma scintigraphy to measure penetration index of inhaled aerosols. Am Rev Resp Diseases 1989;139:1516–1523.

    Google Scholar 

  12. Perring S, Summers Q, Fleming JS, Nassim MA, Holgate ST. A new method of quantification of the pulmonary regional distribution of aerosols using combined CT and SPECT and its application to nedocromil sodium administered by metered dose inhaler. Br J Radiol 1994;67:46–53.

    Google Scholar 

  13. Fleming JS, Nasim MA, Hashish AH, Bailey AG, Conway J, Holdgate ST, Halson P, Moor E, Mortenen TB. Description of pulmonary deposition of radiolabelled aerosol by airway generation using a conceptual 3D model of lung morphology. J Aerosol Med 1995; 8:297–300.

    Google Scholar 

  14. Perkins AC, Mann, Wilson CG. Three dimensional visualisation of the large bowel: a potential tool for assessing targeted drug delivery and colonic pathology. Eur J Nucl Med 1995; 22:1035–1038.

    Google Scholar 

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  1. RIDER Unit, Dept. of Medical Physics, University Hospital, Queen's Medical Centre, NG7 2UH, Nottingham, UK

    A. C. Perkins

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  1. A. C. Perkins
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Perkins, A.C., Frier, M. Nuclear medicine techniques in the evaluation of pharmaceutical formulations. Pharm World Sci 18, 97–104 (1996). https://doi.org/10.1007/BF00417757

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