Predictive evaluation of pharmaceutical properties of direct compression tablets containing theophylline anhydrate during storage at high humidity by near-infrared spectroscopy

Abstract

BACKGROUND: Theophylline anhydrate (TA) in tablet formulation is transformed into monohydrate (TH) at high humidity and the phase transformation affected dissolution behavior.

OBJECTIVE: Near-infrared spectroscopic (NIR) method is applied to predict the change of pharmaceutical properties of TA tablets during storage at high humidity.

METHODS: The tablet formulation containing TA, lactose, crystalline cellulose and magnesium stearate was compressed at 4.8 kN. Pharmaceutical properties of TA tables were measured by NIR, X-ray diffraction analysis, dissolution test and tablet hardness.

RESULTS: TA tablet was almost 100% transformed into TH after 24 hours at RH 96%. The pharmaceutical properties of TA tablets, such as tablet hardness, 20 min dissolution amount (D20) and increase of tablet weight (TW), changed with the degree of hydration. Calibration models for TW, tablet hardness and D20 to predict the pharmaceutical properties at high-humidity conditions were developed on the basis of the NIR spectra by partial least squares regression analysis. The relationships between predicted and actual measured values for TW, tablet hardness and D20 had straight lines, respectively.

CONCLUSIONS: From the results of NIR-chemometrics, it was confirmed that these predicted models had high accuracy to monitor the tablet properties during storage at high humidity.

Keywords

Storage at high humidity theophylline anhydrate tablet formulation study tablet hardness dissolution test polymorphic transformation hygroscopicity chemometrics

Get full access to this article

View all access options for this article.

References

[1] U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Guidance for industry PAT – A framework for innovative pharmaceutical development, manufacturing, and quality assurance, 2004, available at: http://www.fda.gov/downloads/Drugs/Guidances/ucm070305.pdf.

[2] Puig-Lleixá

Jiménez

Alonso

and Bartrolí

, Polyurethane–acrylate photocurable polymeric membrane for ion-sensitive field-effect transistor based urea biosensors, Analytica Chimica Acta 389 (1999), 179–188.

[3] Otsuka

Abe

Aburada

and Otsuka

, Non-destructive prediction of the drug content of an aspirin suppository by near-infrared spectroscopy, Drug Devel. Ind. Pharm. 36 (2010), 839–844.

[4] Otsuka

, Comparative particle size determination of phenacetin bulk powder by using Kubelka–Munk theory and principal component regression analysis based on near-infrared spectroscopy, Powder Technology 141 (2004), 244–250.

[5] Sheffer

and Higuchi

, Dissolution behavior of crystalline solvated and nonsolvated forms of some pharmaceuticals, J. Pharm. Sci. 52 (1963), 781–791.

[6] Debnath

Predecki

and Suryanarayanan

, Using of glancing angle X-ray powder diffractometry to depth-profile phase transformations during dissolution of indomethacin and theophylline tablets, Pharm. Res. 21 (2004), 149–159.

[7] Debnath

and Suryanarayanan

, Influence of processing-induced phase transformations on the dissolution of theophylline tablets, AAPS PharmSciTech 5(1) (2004), 39–49.

[8] Sandler

Rantanen

Heinämäki

Römer

Marvola

and Yliruusi

, Pellet manufacturing by extrusion-spheronization using process analytical technology, AAPS PharmSciTech 6 (2005), E174–E183.

[9] Salameh

and Taylor

, Physical stability of crystal hydrates and their anhydrates in the presence of excipients, J. Pharm. Sci. 95 (2006), 446–461.

10.

[10] Otsuka

Kaneniwa

Kawakami

and Umezawa

, Effect of surface characteristic of theophylline anhydrate powder on hygroscopic stability, J. Pharm. Pharmacol. 42 (1990), 606–610.

11.

[11] Rodriguez-Hornedo

Lechuga-Ballesteros

and Wu

H.J.

, Phase transition and heterogeneous/epitaxial nucleation of hydrated and anhydrous theophylline crystals, Int. Pharm. 85 (1992), 149–162.

12.

[12] Otsuka

Yamamoto

Abe

and Otsuka

, Effects of polymorphic transformation on pharmaceutical properties of direct compressed tablets containing theophylline anhydrate bulk powder under high humidity, Colloids and Surfaces B: Biointerfaces 102 (2013), 931–936.

13.

[13] InfoMetrix Co., Software manual for Pirouette version 3.11, Woodinville, WA.

14.

[14] Iwamoto

Kawano

and Uozumi

, Introduction of Near Infrared Spectroscopy, Sachi Syobou Co., Tokyo, Japan, 1994.

15.

[15] Hayashi

Sato

and Otsuka

, Real-time monitoring of the drying of extruded-granules in a fluidized bed using near infrared spectroscopy and kinetic evaluation of the drying process, J. Near Infrared Spec. 21 (2013), 107–115. doi:10.1255/jnirs.1040.

16.

[16] Tanabe

Otsuka

and Otsuka

, Theoretical analysis of tablet hardness prediction using chemoinformetric near-infrared spectroscopy, Anal. Sci. 23 (2007), 857–862.

17.

[17] Otsuka

Tanabe

Osaki

Otsuka

and Ozaki

, Chemoinformetrical evaluation of dissolution property of indomethacin tablets by near-infrared spectroscopy, J. Pharm. Sci. 96 (2007), 788–801.

18.

[18] Noyes

A.A.

and Whitney

W.R.

, The rate of solution of solid substances in their own solutions, J. Am. Chem. Soc. 19 (1897), 930–934.