Topical Delivery of Ketorolac Tromethamine via Cataplasm for Inflammatory Pain Therapy

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of inflammatory pain, such as in osteoarthritis. Ketorolac tromethamine is considered to be an NSAID with strong anti-inflammatory and analgesic potency, however, traditional applications, such as oral administration and injections, often induce high systemic exposure, leading to adverse events such as gastric ulceration and bleeding. To address this key limitation, herein we designed and fabricated a topical delivery system for ketorolac tromethamine via cataplasm, which is based on a three-dimensional mesh structure formed by the cross-linking of dihydroxyaluminum aminoacetate (DAAA) and sodium polyacrylate. The viscoelasticity of the cataplasm was characterized by rheological methods and exhibited a “gel-like” elastic property. The release behavior showed a Higuchi model characteristic with a dose dependence. To enhance the skin permeation, permeation enhancers were added and screened utilizing ex vivo pig skin, in which 1,2-propanediol was found to have the optimal permeation-promoting effect. The cataplasm was further applied to a rat carrageenan-induced inflammatory pain model, which showed comparable anti-inflammatory and analgesic effects with oral administration. Finally, the biosafety of the cataplasm was tested in healthy human volunteers, and reduced side effects were achieved as compared to the tablet formulation, which can be ascribed to less systemic drug exposure and lower blood drug concentrations. Therefore, the constructed cataplasm can reduce the risk of adverse events while maintaining efficacy, thus serving as a better alternative for the treatment of inflammatory pain, including osteoarthritis.

Polyacrylate–Cholesterol Amphiphilic Derivative: Formulation Development and Scale-up for Health Care Applications

“…More recent literature offers interesting examples of PAA-based systems implemented in topical drug delivery. However, in these cases, PAA was mainly used as a viscosity enhancer, requiring different excipients [ 54 ] or cross-linking [ 55 ] to maintain the structural stability and integrity of the formulation. In contrast, PAAbCH is versatile by combining its attributes to simplify formulation composition.…”

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Modulates Inflammatory Pain in Mice

“…For example, in the regulation of respiratory activity, the PBN projects to the nucleus tractus solitarius (NST), preBöt complex, rostral ventral respiratory group (rVRG), etc. [7,35]. In pain regulation, the PBN mainly projects to the CeA, BNST, PAG, intralaminar thalamic nucleus (ILN), ventral tegmental area (VTA), etc.…”

“…Inflammatory pain is one of the major contributors to the health care burden and is associated with many chronic diseases [5,6]. Despite the high prevalence and severity of inflammatory pain, the medications currently available to treat inflammatory pain are unsatisfactory, such as nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and some adjuvant medications [7]. The combination of different drugs with different mechanisms of action improves the therapeutic effect, but their use is limited due to their increased risk of side effects [8].…”

Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis

“…Currently, in clinical settings, pharmacotherapy for fungal keratitis includes effective antifungal agents combined with anti-inflammatory medications. , These includes the use of topical natamycin, amphotericin B, fluconazole, voriconazole aided with dexamethasone, diclofenac, and ketorolac like NSAIDs. − In a prospective clinical study, voriconazole was identified as an effective and well-tolerated drug for the management of stubborn corneal ulcers resulting from Aspergillus keratitis . However, severe inflammatory FK often associated with corneal wounds which progresses to ulcers and eventually leaves corneal scar which leads to vision impairment. ,, Corneal scarring stands as a primary contributor to the loss of corneal transparency and resultant blindness on a global scale .…”