Simultaneous Determination of Multiple Medications in Fixed-Dose Combinations Using Chemometrics and Artificial Neuron Networks

Fixed-dose combination (FDC) formulations are medicines that contain two or more active ingredients in a single dosage. FDCs can be cost-effective treatments, but also can be ineffective or result in negative side effects for the user because dosage alternation of one drug isn’t possible without changing the other drug (1,2). Because of this challenge, more research is being done on FDCs to increase effectiveness and reduce the potential side effects.

Recently, a research team from Cairo University explored a new way to simultaneously determine multiple medications within FDC formulations. The research team, led by Eman A. Mostafa, introduced a new approach that combined UV spectrophotometry with advanced chemometric techniques and artificial neuron networks (ANNs) (3). Their findings were published in the Journal of Chemometrics (3).

In the past, separate models for each substance were required when determining the concentration of individual components within FDC formulations (3). Mostafa's team tested out a new process. They opted to employ chemometric methods, such as principal component regression (PCR), partial least-squares (PLS), classical least-squares (CLS), and radial basis function–artificial neural network (RBF-ANN), to improve efficiency and accuracy in the process (3).

The researchers validated their method using laboratory-prepared combinations of aspirin, clopidogrel, and either atorvastatin or rosuvastatin. By analyzing absorbance data matrices within the UV spectrum range of 250–280 nm, they were able to accurately predict concentrations using calibration or regression techniques (3).

The RBF-ANN model, equipped with 151 neurons in the input layer, 2 hidden layers, and 3 output neurons, enabled the simultaneous determination of aspirin, clopidogrel, and either atorvastatin or rosuvastatin within FDC formulations (3).

The approach the researchers used proved to be advantageous in a couple important ways. Apart from improved efficiency, the approach used in this study was environmentally friendly (2). The "green profile" of the developed methods was evaluated and compared favorably with previously reported spectrophotometric techniques (3).

The implications of this research are significant for pharmaceutical analysis and quality control. By streamlining the determination process of multiple medications within FDC formulations, this method promises to enhance efficiency and accuracy in drug manufacturing and regulatory compliance (3).

Mostafa's team demonstrated the effectiveness of their approach by successfully applying it to FDC dosage forms containing the cited medications (2). This marks a notable advancement in pharmaceutical analysis, with potential applications across various therapeutic areas where combination therapies are prevalent (3).

As the demand for FDC formulations continues to rise, analytical techniques like the one presented in the study will continue to be developed and improved upon.

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References

(1) Thangaraju, P.; Varthya, S. B.; Venkatesan, S. Fixed-dose Combinations: An Essential for Rational Preparation. Indian J. Pharmacol. 2021, 53 (2), 170–172. DOI: 10.4103/ijp.IJP_133_119

(2) Gautam, C. S.; Saha, L. Fixed Dose Drug Combinations (FDCs): Rational or Irrational: A View Point. Br. J. Clin. Pharmacol. 2008, 65 (5), 795–796. DOI: 10.1111/j.1365-2125.2007.03089.x

(3) AlSawy, N. S.; ElKady, E. F.; Mostafa, E. A. Novel Eco-friendly Methods for Simultaneous Determination of Aspirin, Clopidogrel, and Atorvastatin or Rosuvastatin in their Fixed-dose Combination Using Chemometric Techniques and Artificial Neural Networks. J. Chemom. 2023, ASAP. DOI: 10.1002/cem.3474