DISCRIMINATORY POTENTIAL OF BIPHASIC MEDIUM OVER COMPENDIAL AND BIORELEVANT MEDIUM FOR ASSESSMENT OF DISSOLUTION BEHAVIOR OF TABLETS CONTAINING MELOXICAM NANOPARTICLES

  • Ranjith Anishetty School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
  • Sachin Kumar Singh School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
  • Varun Garg School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
  • Ankit Kumar Yadav School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
  • Monica Gulati School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
  • Bimlesh Kumar School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
  • Narendra kumar Pandey School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
  • Rakesh Narang School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
  • Amit Mittal School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

Abstract

ABSTRACT
Objective: Dissolution test serves as a quality control tool for assessment of drug release from dosage form as well as a research tool to optimize new
formulations. The existing guidelines by FDA, EMA, ICH, USP, etc., describe specifications for the dissolution of immediate release as well as modified
release oral dosage form. However, none of them have discussed about the discriminatory potential of the medium to differentiate release profile of two
or more products that are pharmaceutically equivalent. It is pertinent to add here that the pharmaceutical equivalents are not always bioequivalent.
Hence, a discriminatory dissolution procedure is a must requirement to differentiate the release behavior of drug from a pharmaceutically equivalent
product that contains different types and amount of excipient in the formulation. This also becomes more cumbersome when it is desirable for
prediction of in vivo behavior of a drug when it is converted into a novel delivery system like nanoparticles. The reason could be the presence of
excipients used to formulate drug nanoparticles into solid oral dosage form, may change the drug disintegration as well as dissolution behavior, which
ultimately may lead to altered bioavailability.
Methods: In this study, the nanoparticles of meloxicam were prepared using wet media milling and the milled samples were dried using spray drier.
The dried nanoparticles were converted into tablet dosage form by varying the type of diluent. To one batch lactose was used and another one was
containing dicalcium phosphate (DCP). The assessment of release of meloxicam from these two batches was evaluated in various dissolution media.
Results: The study revealed that in all the cases the nanoparticulate tablets of Batch 1 have given increased dissolution profile as compared to
marketed formulation (Muvera
), Batch 2 and controlled tablets of meloxicam. This proved that the excipients also play a major role in the release
behavior of drug otherwise if it was not so, the nanoparticulate tablets of Batch 1 and Batch 2 would have given the same dissolution profile in all the
tried media. Batch 1 containing lactose with a higher surface area provided more and rapid wetting of the drug by the dissolution media compared to
Batch 2 that contained DCP as a major diluent.
®
Conclusion: Among all the dissolution media tried to evaluate the discriminatory power and simulation with a biorelevant medium, the biphasic
medium of pH 1.8, 4.8 and 6.8 has promised to simulate with biorelevant media. However, the medium of pH 6.8 has shown the best dissolution profile.
Keywords: Solubility, Compendial media, Biphasic media, Dissolution, Meloxicam.

References

REFERENCES
1. Han HK, Choi HK. Improved absorption of meloxicam via salt formation
with ethanolamines. Eur J Pharm Biopharm 2007;65(1):99-103.
2. Türck D, Roth W, Busch U. A review of the clinical pharmacokinetics
of meloxicam. Br J Rheumatol 1996;35 Suppl 1:13-6.
3. Davies NM, Skjodt NM. Clinical pharmacokinetics of meloxicam.
A cyclo-oxygenase-2 preferential nonsteroidal anti-inflammatory drug.
Clin Pharmacokinet 1999;36(2):115-26.
4. Busch U, Schmid J, Heinzel G, Schmaus H, Baierl J, Huber C, et al.
Pharmacokinetics of meloxicam in animals and the relevance to
humans. Drug Metab Dispos 1998;26(6):576-84.
5. Hanft G, Türck D, Scheuerer S, Sigmund R. Meloxicam oral suspension:
A treatment alternative to solid meloxicam formulations. Inflamm Res
2001;50 Suppl 1:S35-7.
6. Narjes H, Türck D, Busch U, Heinzel G, Nehmiz G. Pharmacokinetics
and tolerability of meloxicam after i.m. administration. Br J Clin
Pharmacol 1996;41(2):135-9.
7. Euller-Ziegler L, Vélicitat P, Bluhmki E, Türck D, Scheuerer S,
Combe B. Meloxicam: A review of its pharmacokinetics, efficacy
and tolerability following intramuscular administration. Inflamm Res
2001;50 Suppl 1:S5-9.
8. Available from: http://www.drugbank.ca/drugs/DB00814. [Last
accessed on 2016 Mar 22].
9. Luger P, Daneck K, Engel W, Trunmlitz G, Wagner K. Structure and
physicochemical properties of meloxicam, a new NSAID. Eur J Pharm
Sci 1996;4:175-87.
10. Seedher N, Bhatia S. Solubility enhancement of Cox-2 inhibitors using
various solvent systems. AAPS PharmSciTech 2003;4(3):E33.
11. Buchi N, Chowdary KP, Murthy KV, Satyanarayana V, Hayman AR,
Becket G. Physicochemical characterization and dissolution properties
of meloxicam-cyclodextrin binary systems. J Pharm Biomed Anal
2004;35:75-86.
12. Ghorab MM, Abdel-Salam HM, El-Sayad MA, Mekhel MM. Tablet
formulation containing meloxicam and b-cyclodextrin: Mechanical
characterization and bioavailability evaluation. AAPS PharmSciTech
2004;5(4):E59.
13. Sharma S, Sher P, Badve S, Pawar AP. Adsorption of meloxicam on
porous calcium silicate: Characterization and tablet formulation. AAPS
PharmSciTech 2005;6(4):E618-25.
14. Vijaya Kumar SG, Mishra DN. Preparation and evaluation of solid
dispersion of meloxicam with skimmed milk. Yakugaku Zasshi
2006;126(2):93-7.
15. Kesisoglou F, Panmai S, Wu Y. Nanosizing – Oral formulation
development and biopharmaceutical evaluation. Adv Drug Deliv Rev
2007;59:631-44.
16. Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: A promising
drug delivery strategy. J Pharm Pharmacol 2004;56(7):827-40.
17. Möschwitzer J, Achleitner G, Pomper H, Müller RH. Development
of an intravenously injectable chemically stable aqueous omeprazole
formulation using nanosuspension technology. Eur J Pharm Biopharm
2004;58:615-9.
18. Hillery AM, Lloyd AW, Swarbrick J. Drug Delivery and Targeting for
Pharmacists and Pharmaceutical Scientists. 1
ed. New York: Taylor
and Francis; 1979.
st
19. Dressman JB, Amidon GL, Reppas C, Shah VP. Dissolution testing as
a prognostic tool for oral drug absorption: Immediate release dosage
forms. Pharm Res 1998;15:11-22.
20. Dissolution testing of solid oral dosage forms. In: British Pharmacopoeia.
London: The Statuary Office; 2009. p. A563.
21. The dissolution procedure: Development and validation 1092. In:
United States Pharmacopoeia and National Formulary USP 32–NF 27.
Rockville, MD: The United States Pharmacopoeial Convention, Inc.;
2009. p. 599-604.
22. Hörter D, Dressman JB. Influence of physicochemical properties on
dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev
2001;46(1-3):75-87.
23. Klein S, Wunderlich M, Stippler E, Dressman J. Development of
Dissolution tests on the basis of gastrointestinal physiology. In:
Dressman J, Kramer J, editors. Pharmaceutical Dissolution Testing.
Informa Healthcare. Boca Raton, FL: Taylor & Francis Group, LLC;
2005. p. 193-227.
24. Gross G, Tardio J, Kuhlmann O. Solubility and stability of dalcetrapib
in vehicles and biological media. Int J Pharm 2012;437(1-2):103-9.
25. Anishetty R, Yadav AK, Kaur P, Singare DS, Gulati M, Singh SK.
Formulation, solidification and in vitro evaluation of spraydried
powders containing meloxicam nanoparticles to enhance its

dissolution
rate.
In:
Singh
B,
Kaushik
A,
Mehta
SK,
Tripathi
SK,

editors.
Nanotechnology: Novel Perspectives and Prospects.

New
Delhi,
India:
McGraw
Hill
Education (India) Private Limited;

2015.
p.
636-43.
26. Tukaram BN, Rajagopalan IV, Poddar SI. The effects of lactose,
microcrystalline cellulose and dicalcium phosphate on swelling and
erosion of compressed HPMC matrix tablets: Texture analyzer. Iran J
Pharm Res 2010;9(4):349-58.
27. Ghareeb MM, Mohammed TM. Preparation and characterization of
orodispersibletablets of meclizine hydrochloride by wet granulation
method. Afr J Pharm Pharmacol 2013;7(28):1969-73.
28. The United States Pharmacopeia 30/National Formulary 25. USP 30/
NF 25. USA: United States Pharmacopoeial Convention, Inc.; 2007.
29. Müllertz A. Biorelevant dissolution media. In: Augustijns P,
Brewster ME, editors. Solvent Systems and Their Selection in
Pharmaceutics and Biopharmaceutics. Biotechnology: Pharmaceutical
Aspects. Vol. 6. New York, NY: Springer; 2007. p. 151-77.
30. Dressman J, Krammer J. Pharmaceutical Dissolution Testing. London:
Taylor and Francis Group; 2005.
31. ICH Topic Q 6 A, Specifications: Test Procedures and Acceptance
Criteria for New Drug Substances and New Drug Products: Chemical
Substances. http://www.ema.europa.eu/docs/en_GB/document_library/
Scientific_guideline/2009/09/WC500002823.pdf. [Last accessed on
2015 Oct 19].
32. Heba S, Ghazala A, Dyasb M, Forda JL, Hutcheon GA. In vitro
evaluation of the dissolution behaviour of itraconazole in bio-relevant
media. Int J Pharm 2009;366:117-23.
33. Galia E, Nicolaides E, Hoerter D, Loebenberg R, Reppas C,
Dressman JB. Evaluation of various dissolution media for predicting in
vivo performance of class I and II drugs. Pharm Res 1998;15:698-705.
34. Ahmed IS, Aboul-Einien MH. In vitro and in vivo evaluation of a fastdisintegrating
lyophilized
dry
emulsion tablet
containing griseofulvin.

Eur
J Pharm Sci 2007;32(1):58-68.
35. Marquesm M. Dissolution media simulating fasted and fed states.
Dissolution Technol 2004;11(2):16.
263
Asian J Pharm Clin Res, Vol 9, Issue 4, 2016, 253-264
Anishetty et al.
36. Sangwai M, Vavia P. Amorphous ternary cyclodextrin nanocomposites
of telmisartan for oral drug delivery: Improved solubility and reduced
pharmacokinetic variability. Int J Pharm 2013;453:423-32.
37. Singh SK, Srinivasan KK, Gowthamarajan K, Prakash D, Gaikwad NB.
Investigation of preparation parameters of solid dispersion and
lyophilization technique in order to enhance the dissolution of poorly
soluble glyburide. J Pharm Res 2011;4:2718-23.
38. Singh SK, Srinivasan KK, Singare DS, Gowthamarajan K, Prakash D.
Formulation of ternary complexes of glyburide with hydroxypropyl-βcyclodextrin
and
other solubilizing agents
and their effect
on
release
behavior
of glyburide in aqueous and buffered
media at different

agitation
speeds. Drug Dev Ind Pharm 2012;38:1328-36.
39. Zoeller T, Klein S. Simplified biorelevent media for screening
dissolution performance of poorly soluble drugs. Dissolution Technol
2007;14(4):8-13.
40. Gowthamarajan K, Singh SK. Dissolution testing for poorly soluble
drugs: A continuing perspective. Dissolution Technol 2010;17(3):24-32.
41. Heigoldt U, Sommer F, Daniels R, Wagner KG. Predicting in vivo
absorption behavior of oral modified release dosage forms containing
pH-dependent poorly soluble drugs using a novel pH-adjusted biphasic
in vitro dissolution test. Eur J Pharm BioPharm 2010;76:105-11.
42. Grundy JS, Anderson KE, Rogers JA, Foster RT. Studies on dissolution
testing of the nifedipine gastrointestinal therapeutic system. I. Description
of a two-phase in vitro dissolution test. J Control Release 1997;48:1-8.
43. Smith RN, Hansch C, Ames MM. Selection of a reference partitioning
system for drug design work. J Pharm Sci 1975;64:599-606.
Statistics
231 Views | 475 Downloads
How to Cite
Anishetty, R., S. K. Singh, V. Garg, A. K. Yadav, M. Gulati, B. Kumar, N. kumar Pandey, R. Narang, and A. Mittal. “DISCRIMINATORY POTENTIAL OF BIPHASIC MEDIUM OVER COMPENDIAL AND BIORELEVANT MEDIUM FOR ASSESSMENT OF DISSOLUTION BEHAVIOR OF TABLETS CONTAINING MELOXICAM NANOPARTICLES”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 4, July 2016, pp. 253-64, https://innovareacademics.in/journals/index.php/ajpcr/article/view/12086.
Section
Original Article(s)

Most read articles by the same author(s)