A Stability-Indicating RP-HPLC-UV Method for Determination and Chemical Hydrolysis Study of a Novel Naproxen Prodrug

Abstract

A new naproxen amide prodrug was synthesized and spectrally characterized and a simple, precise, and accurate stabilityindicating RP-HPLC method was developed and validated for determination and chemical hydrolysis study of the prodrug. Forced degradation studies were conducted as per the International Conference on Harmonization (ICH) guidelines to establish the stability-indicating power of the method. Separations were performed on a C 18 column (150 × 4.6 mm i.d., 5 m p.s.). The mobile phase consisted of acetonitrile and phosphate buffer pH 4.0 in the ratio 60 : 40. The flow rate and injection volume were 1.0 mL/min and 15 L, respectively. The peaks were monitored at 272 nm. The average retention time is 5.136 min. The linearity of the method was investigated in the range of 10-50 g/mL and 2 was found to be larger than 0.9987. The LOD and LOQ were found to be 1.853 and 5.615 g/mL, respectively. Results indicated that the degradants are well resolved and separated from the prodrug. Hydrolysis kinetics studies were carried out in buffer solutions (pH 1.2, 5.5 and 7.4) to establish the fate of the prodrug. The half-lives in the respective buffers were 23.5, 262, and 334 hours indicating sufficient stability to attain the goal of oral delivery.

Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

“…It is reported that a promising anti-inflammatory compounds were synthesized by condensation of salicylic acid carbohydrazide with substituted Isatin (Figure 8) [28]. In continuation of our efforts to develop safe and effective anti-inflammatory compounds [29, 30], we designed and synthesized new Diclofenac-Isatin hybrids and screened them for in vivo anti-inflammatory activity with molecular docking studies.…”

Molecular Docking, Pharmacokinetic, and DFT Calculation of Naproxen and its Degradants

“…Naproxen is a naphthalene nucleus bearing nonsteroidal anti-pyratic and anti-inflammatory drug, that plays key role against cyclooxygenase (COX) leading to suppress prostaglandins accumulation caused by various diseases [1,2]. It has undesirable side effects upon routine medication due to free form of terminal acid group.…”

“…It has undesirable side effects upon routine medication due to free form of terminal acid group. A bunch of modification focused on terminal acid group protection or prodrug derivatization in order to minimize the secondary effect [1][2][3]. Several degradative studies suggested to investigate the nature of degradant in the different chemical and physical environment [4,5].…”

Isocratic Reverse-Phase HPLC Method for Determination of Aspirin, Paracetamol, and Naproxen

“…Therefore, there is growing research on the simultaneous analysis of drug mixtures using chromatography. HPLC methods have been used for the quantitative and qualitative analysis of NSAIDs [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Isocratic methods are used to determine one or two compounds, while gradient methods are used for multiple drugs [26].…”