Physicochemical characterization andin vivo evaluation of thermosensitive diclofenac liquid suppository

Abstract

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

“…In our study, the gelation temperature of 17% w/w poloxamer solutions increased with increasing diclofenac sodium concentrations of 1% w/v and above, and the gelation temperature of 20% w/w poloxamer solutions increased with increasing diclofenac sodium concentrations of 1.5% w/v and above (Figure 4). These results are in agreement with previous studies, which reported large increases in gelation temperature of mixtures of poloxamers 407 and 188 with the addition of 2.5% diclofenac sodium [18,39]. In another study, addition of anti-inflammatory drugs to poloxamer 407 gels resulted in a small decrease in gelation temperature with concentrations below 0.5% w/w of naproxen or indomethacin.…”

“…A series of studies was conducted to Past studies have been conducted exploring thermosensitive polymers as potential formulation ingredients to deliver analgesic compounds, but the delivery of an analgesic compound topically to a chronic wound site has not yet been adequately explored. A series of studies was conducted to explore poloxamer 407 as an ingredient in a suppository formulation for the prolonged systemic delivery of diclofenac sodium [18]. Additionally, poloxamer 407 has been studied for use in a vehicle for local injection of a prolonged dose of lidocaine hydrochloride [19].…”

Achievements in Thermosensitive Gelling Systems for Rectal Administration

“…Furthermore, the simplicity of administration and the ability to reduce discomfort to the rectal mucosa has contributed to the development of these dosage forms [ 38 , 39 ].…”

“…The hydrogen bonds break and the hydrophilic chains dissolve as the temperature increases. Poloxamer gelation is associated with a polymer dehydration process, which increases chain friction and entanglement while also producing hydrophobic association [ 3 , 38 , 47 , 48 ]. Poloxamers are also known for their compatibility with other compounds, high solubilization capacity of various active ingredients and good characteristics for active ingredient prolonged release [ 3 , 43 , 49 , 50 ].…”

“…Despite many benefits, poloxamer hydrogels do not possess or have weak bioadhesive properties. In addition, they suffer a major disadvantage, which is low mechanical strength and high water permeability, limiting their use as a thermosensitive matrix [ 38 ]. If mucoadhesive properties are required, poloxamer must be formulated with other bioadhesive polymers.…”