Quality by design approach of a pharmaceutical gel manufacturing process, part 2: near infrared monitoring of composition and physical parameters.

We applied the principles of quality by design to the production process of a pharmaceutical gel by using the near infrared spectroscopy (NIRS) technique in combination with multivariate chemometric tools. For this purpose, we constructed a D-optimal experimental design having normal operational condition (NOC) batches as central point. The primary aim here was to develop an expeditious NIRS method for determining the composition of a pharmaceutical gel and assess the temporal changes in major physical factors affecting the quality of the product (specifically, viscosity and pH). Gel components were quantified by using partial least squares (PLS) calibration models of the PLS1 type. The study was completed by using the batch statistical process control method to compare product batches included in the experimental design with NOC batches. Similarities and differences between the two types of batches were identified by using control charts for residuals (Q-statistic) and Hotteling's T2 (D-statistic). The ensuing models, which were subject to errors less than 5%, allowed the gel production process to be effectively monitored. As shown in this work, the NIRS technique is a highly suitable tool for process analytical technology.

[1]  Svante Wold,et al.  Modelling and diagnostics of batch processes and analogous kinetic experiments , 1998 .

[2]  H. Ramon,et al.  Towards development of on-line soil moisture content sensor using a fibre-type NIR spectrophotometer , 2005 .

[3]  John F. MacGregor,et al.  Multivariate SPC charts for monitoring batch processes , 1995 .

[4]  X. Zhou,et al.  Moisture determination in hygroscopic drug substances by near infrared spectroscopy. , 1998, Journal of pharmaceutical and biomedical analysis.

[5]  Diane J Burgess,et al.  Quality by design approach to understand the process of nanosuspension preparation. , 2009, International journal of pharmaceutics.

[6]  Near infrared transflectance spectroscopy: determination of dexketoprofen in a hydrogel. , 2002, Journal of pharmaceutical and biomedical analysis.

[7]  Vincent W. Uhl,et al.  Mixing: Theory and Practice , 1986 .

[8]  N. Rodríguez-Hornedo,et al.  Rheological Characterization of Topical Carbomer Gels Neutralized to Different pH , 2004, Pharmaceutical Research.

[9]  Robert A. Lodder,et al.  Near-Infrared Spectroscopic Determination of Residual Moisture in Lyophilized Sucrose Through Intact Glass Vials , 1989, Pharmaceutical Research.

[10]  Theodora Kourti,et al.  Process Analytical Technology Beyond Real-Time Analyzers: The Role of Multivariate Analysis , 2006 .

[11]  R. E. Aries,et al.  A Demonstration of Truly Remote In-Line Near-Infrared Process Analysis , 1992 .

[12]  Emil W. Ciurczak.  Growth of near-infrared spectroscopy in pharmaceutical and medical sciences , 2002, SPIE BiOS.

[13]  M Blanco,et al.  Near-infrared libraries in the pharmaceutical industry: a solution for identity confirmation. , 2001, The Analyst.

[14]  Edward G. Schilling,et al.  Juran's Quality Handbook , 1998 .

[15]  D. Massart,et al.  On-Line Monitoring of Powder Blending with Near-Infrared Spectroscopy , 1998 .

[16]  N. Rodríguez-Hornedo,et al.  Fourier transform infrared spectroscopy for the analysis of neutralizer-carbomer and surfactant-carbomer interactions in aqueous, hydroalcoholic, and anhydrous gel formulations , 2004, The AAPS Journal.

[17]  M. Blanco,et al.  Characterization and analysis of polymorphs by near-infrared spectrometry , 2004 .

[18]  I. Last,et al.  Development and transferability of near-infrared methods for determination of moisture in a freeze-dried injection product. , 1993, Journal of pharmaceutical and biomedical analysis.

[19]  James K. Drennen,et al.  PHARMACEUTICAL APPLICATIONS OF NEAR-INFRARED SPECTROMETRY , 1993 .

[20]  C. Rhodes,et al.  Near-Infrared Spectroscopy as a Nondestructive Alternative to Conventional Tablet Hardness Testing , 2004, Pharmaceutical Research.

[21]  I. C. Zampini,et al.  Design and quality control of a pharmaceutical formulation containing natural products with antibacterial, antifungal and antioxidant properties. , 2009, International journal of pharmaceutics.

[22]  E. Ciurczak.  Uses of near-infrared spectroscopy in pharmaceutical analysis , 1987 .

[23]  John F. MacGregor,et al.  Multi-way partial least squares in monitoring batch processes , 1995 .

[24]  H. Bjørsvik.  Reaction Monitoring in Explorative Organic Synthesis Using Fiber-Optical NIR Spectroscopy and Principal Component Analysis , 1996 .

[25]  H. Wu,et al.  Quality-by-design (QbD): an integrated approach for evaluation of powder blending process kinetics and determination of powder blending end-point. , 2009, Journal of pharmaceutical sciences.

[26]  T. Isaksson,et al.  Determination of Particle Size in Powders by Scatter Correction in Diffuse Near-Infrared Reflectance , 1988 .

[27]  J B Callis,et al.  Noninvasive method for monitoring ethanol in fermentation processes using fiber-optic near-infrared spectroscopy. , 1990, Analytical chemistry.

[28]  Huiquan Wu,et al.  Quality-by-design (QbD): an integrated multivariate approach for the component quantification in powder blends. , 2009, International journal of pharmaceutics.

[29]  Katherine A. Bakeev.  Process analytical technology : spectroscopic tools and implementation strategies for the chemical and pharmaceutical industries , 2010 .

[30]  Pedro Hernandez-Abad,et al.  Quality by design case study: an integrated multivariate approach to drug product and process development. , 2009, International journal of pharmaceutics.

[31]  R. Schirmer.  Modern methods of pharmaceutical analysis , 1982 .

[32]  M. Kemper,et al.  Quantifying Crystalline Form Composition in Binary Powder Mixtures Using Near-Infrared Reflectance Spectroscopy , 2000, Pharmaceutical development and technology.

[33]  Use of FT-NIR transmission spectroscopy for the quantitative analysis of an active ingredient in a translucent pharmaceutical topical gel formulation , 2001, AAPS PharmSci.