DESIGN OF DISSOLUTION STUDY PROTOCOL FOR PULMONARY DOSAGE FORMS: CRITERIA FOR SELECTION OF BIO-RELEVANT DISSOLUTION MEDIUM

SAUMYAJYOTI DAS; PRASENJIT SARKAR; SUTAPA BISWAS MAJEE

doi:10.22159/ajpcr.2022.v15i2.43887

Authors

SAUMYAJYOTI DAS Department of Pharmaceutical Technology, Division of Pharmaceutics, NSHM Knowledge Campus, Kolkata-Group of Institutions, Kolkata, West Bengal, India. https://orcid.org/0000-0002-2554-355X
PRASENJIT SARKAR Department of Pharmaceutical Technology, Division of Pharmaceutics, NSHM Knowledge Campus, Kolkata-Group of Institutions, Kolkata, West Bengal, India. https://orcid.org/0000-0002-6864-967X
SUTAPA BISWAS MAJEE Department of Pharmaceutical Technology, Division of Pharmaceutics, NSHM Knowledge Campus, Kolkata-Group of Institutions, Kolkata, West Bengal, India. https://orcid.org/0000-0001-6325-0339

DOI:

https://doi.org/10.22159/ajpcr.2022.v15i2.43887

Keywords:

Airway surface liquid, Andersen cascade impactor, Bio-relevant dissolution medium, Dipalmitoyl phosphatidylcholine, DissolvIt, Lung surfactant protein, Next generator impactor, Pulmonary dosage forms, Simulated lung fluid, Transwell

Abstract

Pulmonary dosage forms constitute an important route of drug delivery for systemic absorption of drugs in management of respiratory diseases as well as diseases such as diabetes, migraine, osteoporosis, and cancer. Performance of different pulmonary dosage forms is greatly influenced by aerodynamic particle size distribution of inhalable particles, spray pattern, fraction of dose actually deposited on pulmonary epithelium, dissolution of active pharmaceutical ingredient and ultimately absorption across pulmonary barriers. In vitro dissolution study should be designed to predict in vivo performance precisely, providing key information on bioavailability and establishing in vitro-in vivo correlation. To obtain meaningful data from dissolution study, focus should be on composition of dissolution medium, dissolution conditions and dissolution test apparatus. For pulmonary dosage forms, selection of physiologically relevant dissolution medium, mimicking lung fluid (LF) is a challenging task. Attempts are being made to develop bio-relevant dissolution medium to overcome the limitations associated with use of conventional media lacking lung surfactant proteins, or several salts normally present in pleural fluid. Use of simulated LFs can give a better understanding of the release mechanisms and possible in vivo behavior of pulmonary dosage forms thereby enhancing the predictive capability of the dissolution testing. In the review, efforts have been taken to provide comprehensive information on composition, physicochemical characteristics and functions of physiological LF, challenges associated with the design and development of dissolution study protocol for pulmonary dosage forms, criteria for selection of an appropriate bio-relevant dissolution medium, comparative study on various reported bio-relevant dissolution media and dissolution apparatuses employed for in vitro characterization of performance of pulmonary dosage forms.

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References

Azarmi S, Roa WH, Lobenberg R. Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev 2008;60:863-75.

Sung JC, Pulliam BL, Edwards DA. Nanoparticles for drug delivery to the lungs. Trends Biotechnol 2007;25:563-70.

Jaafar-Maalej C, Elaissari A, Fessi H. Lipid-based carriers: Manufacturing and applications for pulmonary route. Expert Opin Drug Deliv 2012;9:1111-27.

Beck-Broichsitter M, Gauss J, Packhaeuser CB, Lahnstein K, Schmehl T, Seeger W, et al. Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. Int J Pharm 2009;367:169-78.

Beck-Broichsitter M, Kleimann P, Gessler T, Seeger W, Kissel T, Schmehl T. Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb® Pro: Formulation aspects and nanoparticle stability to nebulization. Int J Pharm 2012;422:398-408.

Paranjpe M, Muller-Goymann S. Nanoparticle-mediated pulmonary drug delivery: A review. Int J Mol Sci 2014;15:5853-6.

David E, Geller MD. Comparing clinical features of the nebulizer, metered-dose inhaler and dry powder inhaler. Respir Care 2005;50:1313-21.

Anderson PJ. History of aerosol therapy: Liquid nebulization to MDIs to DPIs. Respir Care 2005;50:1139-49.

Rau JL. The inhalation of drugs: Advantages and problems. Respir Care 2005;50:367-82.

Everard ML. Inhaler devices in infants and children: Challenges and solutions. J Aerosol Med 2004;17:186-95.

Thorsson L, Geller D. Factors guiding the choice of delivery device for inhaled corticosteroids in the long-term management of stable asthma and COPD: Focus on budesonide. Respir Med 2005;99:836-49.

Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL, et al. Device selection and outcomes of aerosol therapy: Evidence based guidelines. Chest 2005;127:335-71.

Rau JL. Design principles of liquid nebulization devices currently in use. Respir Care 2002;47:1257-75.

Nikander K, Turpeinen M, Wollmer P. The conventional ultrasonic nebulizer proved inefficient in nebulizing a suspension. J Aerosol Med 1999;12:47-53.

Hendeles L, Hatton RC, Coons TJ, Carlson L. Automatic replacement of albuterol nebulizer therapy by metered-dose inhaler and valved holding chamber. Am J Health Syst Pharm 2005;62:1053-61.

Kumar A, Terakosolphan W, Hassoun M, Vandera KK, Novicky A, Harvey R, et al. A biocompatible synthetic lung fluid based on human respiratory tract lining fluid composition. Pharm Res 2017;34:2454-65.

Pham S, Wiedmann TS. Dissolution of aerosol particles of budesonide in Survanta™, a model lung surfactant. J Pharm Sci 2001;90:98-104.

Son YJ, McConville JT. Preparation of sustained release rifampicin microparticles for inhalation. J Pharm Pharmacol 2012;64:1291-302.

Widmaier E, Raff H, Strang KT. Vander’s Human Physiology. 10th ed. New York: McGraw-Hill; 2005.

Grippi MA. Pulmonary Pathophysiology. 1st ed. Philadelphia, PA: Lippincott, Williams and Wilkins; 1995.

Epstein SK. Anatomy and physiology of tracheostomy. Respir Care 2005;50:476-82.

Ahmed-Nusrath A, Tong JL, Smith JE. Pathways through the nose for nasal intubation: A comparison of three endotracheal tubes. Br J Anaesth 2008;100:269-74.

Minnich DJ, Mathisen DJ. Anatomy of the trachea, carina, and bronchi. Thorac Surg Clin 2007;17:571-85.

Webb EM, Elicker BM, Webb WR. Using CT to diagnose nonneoplastic tracheal abnormalities: Appearance of the tracheal wall. AJR Am J Roentgenol 2000;174:1315-21.

Ugalde P, Miro S, Frechette E, Deslauriers J. Correlative anatomy for thoracic inlet; glottis and subglottis; trachea, carina, and main bronchi; lobes, fissures, and segments; hilum and pulmonary vascular system; bronchial arteries and lymphatics. Thorac Surg Clin 2007;17:639-59.

Haskin PH, Goodman LR. Normal tracheal bifurcation angle: A reassessment. AJR Am J Roentgenol 1982;139:879-82.

Widdicombe J. Regulation of the depth and composition of airway surface liquid. J Anat 2002;201:313-8.

Radivojev S, Zellnitz S, Paudel A, Fröhlich E. Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs. Int J Pharm 2019;556:45-56.

Guagliardo R, Perez-Gil J, De Smedt S, Raemdonck K. Pulmonary surfactant and drug delivery: Focusing on the role of surfactant proteins. J Contr Release 2018;291:116-26.

Bastacky J, Lee CY, Goerke J, Koushafar H, Yager D, Kenaga L, et al. Alveolar lining layer is thin and continuous: Low-temperature scanning electron microscopy of rat lung. J Appl Physiol 1995;79:1615-28.

Lindert J, Perlman CE, Parthasarathi K, Bhattacharya J. Chloride-dependent secretion of alveolar wall liquid determined by optical-sectioning microscopy. Am J Respir Cell Mol Biol 2007;36:688-96.

Bhattacharya S, Glucksberg MR, Bhattacharya J. Measurement of lung microvascular pressure in the intact anesthetized rabbit by the micropuncture technique. Circ Res 1989;64:167-72.

Lai-Fook SJ. Perivascular interstitial fluid pressure measured by micropipettes in isolated dog lung. J Appl Physiol 1982;52:9-15.

Ying X, Qiao R, Ishikawa S, Bhattacharya J. Removal of albumin microinjected in rat lung perimicrovascular space. J Appl Physiol 1994;77:1294-302.

Nicolaysen G, Staub NC. Time course of albumin equilibration in interstitium and lymph of normal mouse lungs. Microvasc Res 1975;9:29-37.

Hollenhorst M, Richter K, Fronius M. Ion transport by pulmonary epithelia. J Biomed Biotechnol 2011;15:1-9.

Manzanares D, Gonzalez C, Ivonnet P, Chen RS, Valencia-Gattas M, Conner GE, et al. Functional apical large conductance, Ca2+-activated, and voltage dependent K+ channels are required for maintenance of airway surface liquid volume. J Biol Chem 2011;286:19830-9.

Mall M, Bleich M, Greger R, Schreiber R, Kunzelmann K. The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways. J Clin Invest 1998;102:15-21.

Burch LH, Talbot CR, Knowles MR, Canessa CM, Rossier BC, Boucher RC. Relative expression of the human epithelial Na+ channel subunits in normal and cystic fibrosis airways. Am J Physiol 1995;269:511-8.

Schwiebert EM, Kizer N, Gruenert DC, Stanton BA. GTP-binding proteins inhibit cAMP activation of chloride channels in cystic fibrosis airway epithelial cells. Proc Natl Acad Sci U S A 1992;89:10623-7.

Mitchell JP, Nagel MW. Cascade impactors for the size characterization of aerosols from medical inhalers: Their use and limitations. J Aerosol Med 2003;16:341-77.

Uddin MD, Hossain MD, Mamun AA, Zaman S, Asaduzzaman M, Rashid M, et al. Pharmacopoeial standards and specifications for pharmaceutical aerosols: In-process and finished products quality control tests. Adv Res 2016;6:1-12.

Anand O, Yu LX, Conner DP, Davit BM. Dissolution testing for generic drugs: An FDA perspective. AAPS J 2011;13:328-35.

Hamm H, Kroegel C, Hohlfield J. Surfactant: A review of its function and its relevance in adult respiratory disorders. Respir Med 1996;90:251-70.

Rohrschneider M, Bhagwat S, Krampe R, Michler V, Breitkruetz J, Hocchaus G. Evaluation of the transwell system for characterization of dissolution behavior of inhalation drugs: Effects of membrane and surfactant. Mol Pharm 2015;12:2618-24.

Eedara BB, Tucker IG, Das SC. In vitro dissolution testing of respirable size anti-tubercular drug particles using a small volume dissolution apparatus. Int J Pharm 2019;559:235-44.

Gerde P, Malmlof M, Havsborn L, Sjöberg CO, Ewing P, Eirefelt S, et al. DissolvIt: An in vitro method for simulating the dissolution and absorption of inhaled dry powder drugs in the lungs. Assay Drug Dev Technol 2017;15:77-88.

May S, Jensen B, Weiler C, Wolkenhauer M, Schneider M, Lehr CM. Dissolution testing of powders for inhalation: Influence of particle deposition and modeling of dissolution profiles. Pharm Res 2014;31:3211-24.

Arora S, Haghi M, Loo CY, Traini D, Young PM, Jain S. Development of an inhaled controlled release voriconazole dry powder formulation for the treatment of respiratory fungal infection. Mol Pharm 2015;12:2001-9.

Haghi M, Traini D, Bebawy M, Young PM. Deposition, diffusion and transport mechanism of dry powder microparticulate salbutamol at the respiratory epithelia. Mol Pharm 2012;9:1717-26.

Arora D, Shah KA, Halquist MS, Sakagami M. In vitro aqueous fluid-capacity-limited dissolution testing of respirable aerosol drug particles generated from inhaler products. Pharm Res 2010;27:786-95.

Pritchard RJ, Ghio AJ, Lehmann JR, Winsett DW, Tepper JS, Park P, et al. Oxidant generation and lung injury after particulate air pollutant exposure increase with the concentrations of associated metals. Inhal Toxicol 1996;8:457-77.

Vallyathan V, Pack D, Leonard S, Lawson R, Schenker M, Castranova V. Comparative in vitro toxicity of grape and citrus farm dusts. J Toxicol Environ Health 2007;70:95-106.

Bhagat NB, Yadav AV, Mali SS, Khutale RA, Hajare AA. A review on development of biorelevant dissolution medium. J Drug Deliv Ther 2014;4:140-8.

Margareth RC, Loebenberg R, Almukainzi M. Simulated biological fluids with possible application in dissolution testing. Dissolut Technol 2011;18:15-28.

Gray JE, Plumlee GS, Morman SA, Higueras PL, Crock JG, Lowers HA, et al. In vitro studies evaluating leaching of mercury from mine waste calcine using simulated human body fluid. Environ Sci Technol 2010;44:4782-8.

Ungaro F, Bianca RE, Giovino C, Miro A, Sorrentino R, Quaglia F, et al. Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: In vivo deposition and hypoglycemic activity after delivery to rat lungs. J Control Release 2009;135:25-34.

Yang W, Tam J, Miller DA, Zhou J, McConville JT, Johnston KP, et al. High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers. Int J Pharm 2008;361:177-88.

European Pharmacopoeia. Preparations for inhalation: Aerodynamic assessment of fine particles. In: European Pharmacopoeia, 8e, 309–320. Strasbourg, France: European Directorate for the Quality of Medicines, Council of Europe; 2014.

US Pharmacopeia. Aerosols, Nasal Sprays, Metered‐dose Inhalers and Dry Powder Inhalers, USP 37 NF 32. Rockville, MD: US Pharmacopeia; 2014.

Salama RO, Traini D, Chan HK, Young PM. Preparation and characterisation of controlled release co-spray dried drug-polymer microparticles for inhalation: Evaluation of in vitro release profiling methodologies for controlled release respiratory aerosols. Eur J Pharm Biopharm 2008;70:145-52.

Duret C, Wauthoz N, Sebti T, Vanderbist F, Amighi K. Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties. Int J Pharm 2012;428:103-13.

Davies NM, Feddah MR. A novel method for assessing dissolution of aerosol inhaler products. Int J Pharm 2003;255:175-87.

May S, Kind S, Jensen B, Wolkenhauer M, Schneider M, Lehr CM. Miniature in vitro dissolution testing of powders for inhalation. Dissolut Technol 2015;8:40-51.

Lewis DA, Young PM, Buttini F, Church T, Colombo P, Forbes B, et al. Towards the bioequivalence of pressurized metered dose inhalers: Design and characterization of aerodynamically equivalent beclomethasone dipropionate inhalers with and without glycerol as a non-volatile excipient. Eur J Pharm Biopharm 2013;3486:31-7.

Vengala P, Vanamala R. Nanocrystal technology as a tool for improving dissolution of poorly soluble drug, lornoxicam. Int J Appl Pharm 2018;10:162-8.

Rahul S, Abhinand CR, Nikithareddy B, Jayachandra K, Lakshmi P, Doddayya H, et al. Pharmacoeconomic evaluation of acute exacerbations of chronic obstructive pulmonary disease at a tertiary care teaching hospital in North Karnataka, India. Asian J Pharm Clin Res 2018;11:463-6.

Panda N, Reddy V, Reddy GV, Sultana A. Formulation design and in vitro evaluation of bilayer sustained release matrix tablets of doxofylline. Int J Pharm Pharm Sci 2015;7:74-83.

Anwar N, Jan S, Gul R. Formulation and evaluation of glibenclamide gel for transdermal drug delivery. Int J Curr Pharm Res 2020;12:35-9.

Alshargabi A. In vitro assessment of physicochemical parameters of five generics amlodipine besylate tablets marketed in Yemen. Int J Pharm Pharm Sci 2021;13:15-9.

May S, Jensen B, Wolkenhauer M, Schneider M, Lehr CM. Dissolution techniques for in vitro testing of dry powders for inhalation. Pharm Res 2012;29:2157-8.

Bhattacharyya SN, Wesley JA, Fioritto A, Martin PJ, Babu SR. Dissolution testing of a poorly soluble compound using the flow-through cell dissolution apparatus. Int J Pharm 2002;236:135-7.

Heng D, Cutler DJ, Chan HK, Yun J, Raper JA. What is a suitable dissolution method for drug nanoparticles? Pharm Res 2008;25:1696-8.