Enhancing Bioavailability and Therapeutic Potential of Plant-Based Ibuprofen Formulation

Abstract

Approximately 50% of the active pharmaceutical ingredients (APIs) given orally have low solubility, limiting their bioavailability. One such extensively used examples is ibuprofen (2- (4- (2-methylpropyl) phenyl) propionic acid), a non-steroidal anti-inflammatory drug (NSAID) classified as the Biopharmaceutics Classification System (BCS) II due to its low solubility, high permeability, and limited bioavailability. An important trend in the pharmaceutical industry is the growing use of finely subdivided materials, drugs, to increase dissolution, solubility, and bioavailability. Many APIs are thermosensitive, and therefore nonthermal alternative procedures that can enhance the physicochemical properties of drug-excipient combinations have gained popularity. One such technology is the mechanical formulation through milling, which is becoming increasingly popular. A notable advancement in pharmaceuticals involves the reduction of the percentage of APIs by substituting them with organic compounds. These compounds achieve similar therapeutic goals and fulfill the dietary requirements of consumers. Despite the considerable therapeutic potential of ibuprofen in the treatment of various diseases, its applicability, safety, and long-term use are limited by several factors. In particular, ibuprofen can increase the risk of stomach bleeding and ulcers, posing safety concerns for individuals with kidney or heart disease. Consequently, there is an ongoing demand for plant-based combinations that mitigate the limitations associated with APIs. The model selected for this study is ibuprofen and ginger. Where ginger, a traditional herbal remedy with a long history of treating inflammatory conditions, complements the therapeutic goals of ibuprofen. Ginger shares common attributes 2 with ibuprofen, including antioxidant activity, anti-inflammatory properties, and antibacterial effects. Two phases of the screening processes will be conducted after the establishment of parameters that impact the ibuprofen milling process. These parameters include milling duration, frequency, temperature, ball-to-powder ratio, and the ratio of ibuprofen to plant-based material. The first phase, ball mill parameter optimization, involves fixing these parameters while varying them one at a time. The second phase involves varying the ratios of the components. Several analytical tests will be performed to evaluate the results before and after milling. These include X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and high-performance liquid chromatography (HPLC) to track the release profiles of the prepared samples in various acidic, hydrochloric acid (HCl), and slightly basic, phosphate buffer solution (PBS) medium. The results indicated changes in the physical characteristics of ibuprofen after milling. Analysis of the release profiles for unmilled, milled, and various combinations of ibuprofen-ginger showed that the dissolution rate of milled ibuprofen was improved, showing an enhancement 57% over the unmilled form. Furthermore, among the combinations tested, the mixture containing 80% ibuprofen and ginger 20% exhibited the most effective release, achieving an ibuprofen release of 76% in PBS and 25% in HCl. Together, the findings suggest that grinding reduces the size of the particles and enhances the solubility, while the inclusion of ginger further improves the efficiency of ibuprofen release. We anticipate that this study will pave the way for a series of future projects examining the dynamic interplay between APIs and organic ingredients. By exploring various combinations, our aim is to optimize therapeutic efficacy while minimizing potential side effects. This comprehensive approach holds promise for the advancement of pharmaceutical formulations and the improvement of patient outcomes.