J.R. Ticó

Predicting orally disintegrating tablets formulations of ibuprophen tablets: an application of the new SeDeM-ODT expert system.

This article provides a new innovative tool for pharmaceutical preformulation to predict whether a disintegrant excipient or mixture of powder containing API+excipients is suitable to obtain a bucodispersible tablet by direct compression or not. This innovative tool is the new model SeDeM-ODT that provides the Index of Good Compressibility and Bucodispersibility (IGCB index), which is based on the previous SeDeM expert system that indicates the aptitude of a powder to be compressed. The IGCB index is composed of six main factors (from 15 pharmaceutical raw parameters), which indicate whether a mixture of powder has the aptitude to be compressed by direct compression and at the same time indicates whether these tablets are suitable to be used as a bucodispersible tablet (disintegration time lower than 3 min).

Relationships between surface free energy, surface texture parameters and controlled drug release in hydrophilic matrices

The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, such that the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M which increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets.

Quality by Design approach to understand the physicochemical phenomena involved in controlled release of captopril SR matrix tablets.

The aim of this study is to obtain swelling controlled release matrix tablets of captopril using the Quality by Design methodology (ICH Q8) and to know the transport mechanisms involved in captopril release. To obtain the area of knowledge, the design of experiments studying the effect of two components (HPMC K15M and ethylcellulose) at different levels has been applied, with the captopril dissolution profile as the products most important critical quality attribute (CQA). Different dissolution profiles have been obtained with the design of experiments performed, which is a key factor in the development of controlled release matrix tablets. Kinetic analysis according to the equations of Higuchi and Korsmeyer-Peppas demonstrates that the release mechanism is a mechanism of erosion when the whole percentage of the polymer is ethylcellulose, and a diffusion mechanism when the whole percentage of the polymer is HPMC K15M. The physico-chemical characteristics of the gel layer determine the release rate of captopril. The thickness of the gel layer, the porosity which is formed in the matrix upon contact with water, pore size, the swelling rate, the erosion rate of the matrix, and the physico-chemical characteristics of captopril, are factors related to the kinetic equations described and that allow us to predict the release mechanism of captopril. A new relationship of the kinetic equations governing the in vitro behavior with the physical characteristics of the gel layer of the different formulations has been established. This study shows that the size of water-filled pores and the degree of crosslinking between the chains of HPMC K15M of the matrix are related to the exponent n of the Korsmeyer-Peppas equation and the type of transport of the captopril from within the matrix to the dissolution medium, that is, if the transport is only through water-filled pores, or if a combination of diffusion occurs through water-filled pores with a transport through continuous polymeric networks.

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM diagram expert system has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril direct compression SR matrix tablets. The application of the SeDeM diagram expert system enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM diagram expert system as system responses.

SeDeM expert system a new innovator tool to develop pharmaceutical forms

Abstract Context: The SeDeM expert system is based on the experimental study and quantitative determination of the characterization parameters of powdered substances, the aim being to determine whether a substance is suitable for producing tablets by means of direct compression (DC) technology, thereby reducing the lead time for pre-formulation studies. Additionally, this expert system also provides formulations with a minimum number of excipients. Objective: We used this system to analyze suitable formulas for the production of orodispersible ibuprofen tablets. Method: Twenty-one disintegrants and ibuprophen were characterized using SeDeM methodology. Results: The results indicated that production of ibuprofen tablets by DC would require improvements in the dimension and compressibility factors of the active pharmaceutical ingredient. The expert system analysis provided the specific percentage of disintegrant needed to blend with ibuprofen and a standardized formula of lubricants in order to obtain a powder mix that would successfully produce tablets by DC. The eight formulas proposed by SeDeM were produced and tested in the laboratory. Conclusion: All eight formulas successfully produced tablets by DC, but only four of them could be considered suitable for use as an orodispersible tablet and accomplishes all the pharmaceutical quality parameters. So, in fact, the use of the SeDeM system reduced the time of medicine’s development and therefore the cost of the activity.

Study of Formulation Parameters by Factorial Design in Metoprolol Tartrate Matrix Systems

The study of formulation parameters in hydrophilic matrices of metoprolol tartrate by 23 factorial design was made. We compared the dissolution profiles of two hydrophilic polymers (hydroxypropylmethylcellulose and hydroxyethylcellulose) at high and low concentrations and in the presence or absence of an insoluble excipient (calcium hydrogen phosphate dihydrate). The results showed that the presence of an insoluble excipient influenced almost all of the dissolution parameters.

Method for the development of topical medicinal aerosols using liquified hydrocarbon gas

Low chain liquid hydrocarbons (LH) at room temperature and atmospheric pressure can be used to simulate the effect of gas hydrocarbons (GH) in aerosol systems without the need of using pressured flasks. Samples of different tetracycline formulations were tested with LH and GH in order to study their behaviour and physicochemical stability in the system. The results showed a similar behaviour between samples when LH or GH were used, suggesting the use of LH to simulate the effect of GH introduction in the system, as a useful predictive method for the development of pressured aerosol formulations without using pressured containers in early steps of the process, such as pre-formulation studies.

Improving tablet coating robustness by selecting critical process parameters from retrospective data

Abstract Context: Although tablet coating processes are widely used in the pharmaceutical industry, they often lack adequate robustness. Up-scaling can be challenging as minor changes in parameters can lead to varying quality results. Objective: To select critical process parameters (CPP) using retrospective data of a commercial product and to establish a design of experiments (DoE) that would improve the robustness of the coating process. Materials and methods: A retrospective analysis of data from 36 commercial batches. Batches were selected based on the quality results generated during batch release, some of which revealed quality deviations concerning the appearance of the coated tablets. The product is already marketed and belongs to the portfolio of a multinational pharmaceutical company. Results: The Statgraphics 5.1 software was used for data processing to determine critical process parameters in order to propose new working ranges. Discussion and conclusions: This study confirms that it is possible to determine the critical process parameters and create design spaces based on retrospective data of commercial batches. This type of analysis is thus converted into a tool to optimize the robustness of existing processes. Our results show that a design space can be established with minimum investment in experiments, since current commercial batch data are processed statistically.