Amorphous Solid Dispersion of Meloxicam Enhanced Oral Absorption in Rats With Impaired Gastric Motility

Abstract

Meloxicam (MEL) shows a slow onset of action in severe pain patients on account of delayed gastric motility. This study aimed to develop an amorphous solid dispersion (ASD) of MEL to achieve rapid oral absorption in severe pain patients. ASD formulations of MEL with hydroxypropylmethylcellulose (ASD-MEL/HPMC) and polyacrylates and polymethacrylates (ASD-MEL/EUD) were prepared and physicochemically characterized. Oral absorption behavior of MEL samples was also clarified in both normal and propantheline (PPT)-pretreated rats with impaired gastric motility. MEL in the formulations was amorphous, and ASD formulations of MEL exhibited high dissolution behavior in acidic solution. After oral administration of crystalline MEL (1 mg-MEL/kg), a 69% reduction in AUC was observed between normal and PPT-pretreated rats. For orally dosed ASD-MEL/HPMC (1 mg-MEL/kg), there were approximately 9- and 12-fold increases of AUC in normal and PPT-pretreated rats, respectively, in comparison with crystalline MEL (1 mg-MEL/kg). However, the oral absorption behavior of ASD-MEL/EUD (1 mg-MEL/kg) was low and similar to that of crystalline MEL. The infrared spectroscopic study revealed potent interactions between MEL and EUD, possibly leading to marked attenuation of MEL absorption. This ASD approach might provide rapid oral absorption of MEL in severe pain patients, possibly leading to better clinical outcomes.

Ameliorated Stomach Specific Floating Microspheres for Emerging Health Pathologies Using Polymeric Konjac Glucomannan-Based Domperidone

“…SDs of meloxicam exhibited much better dissolution behavior than crystalline meloxicam. It was reported that meloxicam was presented in the amorphous form by SDs which lead to its improved dissolution behavior [ 5 ]. Prepared SDs of chlortetracycline hydrochloride using hydrophilic polymers like PVP and copovidone, Authors reported that SDs increased almost ten-fold chlortetracycline hydrochloride solubility, which they attributed to the amorphous characters of the SDs, proposing the event of intermolecular interactions.…”

Effects of Ingested Water Volume on Oral Absorption of Fenofibrate, a BCS Class II Drug, from Micronized and Amorphous Solid Dispersion Formulations in Rats

“…28) Many in vivo studies during preclinical study adopt a suspension form for oral administration. [29][30][31] We observed, during in vitro dissolution, FEN supersaturation evidenced by the dissolution of the clinical ASD formulation of FEN (Tricor ® Tablets) followed by a rapid decrease in concentration, indicating precipitation (Fig. 1).…”

Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance

“…The largest and the smallest stability constants were observed at phosphate buffer pH 7.4 and at pH 1.2, as depicted in Table 1 . This result could be attributed to the weak acidity nature of the ME which formed a zwitterionic compound with two lower pKa values 1.09 and 4.18 and the solubility in both around 0.6 µg/mL [ 33 ]. For that, ME has a higher solubility in basic conditions and low solubility in acidic media.…”

“…It has poor aqueous solubility and higher permeability, which fall under class II medications in biopharmaceutical classes systems. However, the poorly aqueous solubility and wettability of ME resulted in a slower dissolution rate of the drug, and hence, a lower oral bioavailability concomitant with slowing its onset of action [ 33 , 34 ]. Enhancing the aqueous solubility of ME could facilitate its oral absorption and bioavailability and reduce its onset of action for the treatment of different types of acute pain [ 34 , 35 ].…”