Thermal characterization and stability investigation of sericin and alginate blend loaded with diclofenac sodium or ibuprofen

Highlights

• Diclofenac sodium or ibuprofen loaded sericin/alginate blend was thermally assessed.

• DTA showed no major chemical interaction between the drugs and the matrix.

• HSM allowed to visualize drugs melting and decomposition of polymer matrix.

• Diclofenac sodium formulations were stable under accelerated storage conditions.

Abstract

Developing new pharmaceutical forms from existing drugs has proven to be an alternative in the face of economic and temporal challenges to develop new drugs. In this work, thermal behavior of diclofenac sodium or ibuprofen loaded sericin and alginate particles was evaluated. The thermal phenomena were verified by Thermogravimetric Analysis, Differential Thermal Analysis and Differential Scanning Calorimetry. In addition, the analysis of Hot Stage Microscopy was performed to visualize the thermal phenomena. It was verified that the drugs maintained their original thermal characteristics after their incorporation, which demonstrates no significant interactions between the drugs and the polymeric matrix. The micrographs of Hot Stage Microscopy showed that the drug remains trapped in the particles, even after its melting. The diclofenac sodium particles were also subjected to the accelerated stability test under forced storage conditions (40 ± 2 °C and 75 ± 5% relative humidity) for 6 months, being evaluated the parameters of incorporation efficiency and release of drug in simulated enteric media, after the storage. Considering the results, the particles remained stable in the studied storage conditions, with reproducible incorporation efficiency and release tests.

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs), indicated for treating pain or inflammation, account for approximately 5–10% of all drugs prescribed annually in the world. Nevertheless, they are related to some adverse side effects such as gastrointestinal or kidney toxicity and adverse cardiovascular effects [1]. Among the most commonly used NSAIDs are diclofenac sodium and ibuprofen, which, in addition to the aforementioned adverse effects, also present a low half-life [2]. Such characteristics motivate the development of new pharmaceutical forms for these drugs, making their release controlled.

One way of obtaining modified release systems is by incorporating the drugs into a polymeric matrix [3]. In this sense, the natural blend composed of sericin and alginate has shown to be very promising, with good results for the incorporation of both diclofenac sodium and ibuprofen [4], [5], in addition to other drugs such as ketoprofen [6], furosemide [7] and naproxen [8]. Such blend presents the advantages of biodegradability, biocompatibility and low toxicity, being a very interesting matrix for pharmaceutical application [9].

In the above-mentioned incorporation studies, the obtained particles were characterized as to the ability to incorporate the drugs and the release of these drugs into simulated gastrointestinal environment. In addition, analytical techniques as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and optical microscopy to obtain the size distribution were performed, covering some of the essential analysis in the development of new formulations. Nevertheless, the thermal behavior of these formulations was not properly investigated yet, motivating the present work. Thermal analysis is a significant analytical tool in developing new formulations in order to assess their compatibility, stability, and potential drug-excipients interactions, and along with the XRD is able to provide a complete initial analysis of the physical properties of the formulations [10], [11].

The choice of a good excipient is essential to obtain an effective and therefore easy to administer formulation that enhances the patient's commitment, increases the shelf life and bioavailability of the drug and enables an adequate release profile to be obtained. In this context, hundreds of techniques can be employed, with emphasis on thermogravimetric analysis (TG/DTG), differential thermal analysis (DTA), differential scanning calorimetry (DSC) and hot stage microscopy (HSM), which, together with non-thermal analyzes, allow better evaluation of drug-matrix compatibility [12].

The TG/DTG, DTA and DSC analyzes provide quantitative data on the influence of temperature on the sample. Through them, drug-excipient interactions are observed by shifting the melting point and the decomposition events of the sample [13]. The HSM is a thermo-microscopic technique that allows visual evaluation of the thermal events that occur in the material. Thus, it is used to validate the transitions detected using techniques such as DTA and DSC [12].

In addition to the matter of compatibility between a drug and its excipients, another challenge in the development of new pharmaceutical forms lies in its stability. Such parameter is defined as the state in which an active principle is not degraded due to exposure to specific factors, reflecting the quality of the pharmaceutical form during its shelf life. The stability tests reflect by what means the feature of a drug product alters with time when subjected to controlled environmental factors, as humidity and temperature, further reinforcing the result of previously obtained thermal analyzes [14], [15].

Thus, sericin and alginate particles with sodium diclofenac or ibuprofen incorporated were evaluated for their thermal behavior in the present work. In the literature, it is possible to find studies that evaluated the thermal behavior of systems similar to the one presented in this work, such as diclofenac sodium in alginate matrix [16] or in alginate and chitosan matrix [17]; or ibuprofen loaded in alginate [18] or in an alginate and gellan gum matrix [19]. However, a study involving the matrix of alginate and sericin loaded with diclofenac sodium or ibuprofen, detailing its thermal behavior, as intended in this study, is totally new. For this, the formulations were submitted to TG/DTG, DTA, DSC and HSM analyzes. In addition, the diclofenac sodium formulations were also submitted to an accelerated stability study in controlled temperature and humidity. In this test, the incorporation efficiencies and dissolution assays were obtained and compared to the results presented by Vidart et al. [4] and Freitas et al. [5].