Characterisation of fenofibrate dissolution delivered by a self-microemulsifying drug-delivery system

Abstract

The release rates of FFB from TPGS/Tween 20 systems were faster than those from TPGS/Tween 80 systems at the same K(m) value. In both systems, the release rates of FFB increased with a decrease in the K(m) value. Furthermore, both the release rates and the amounts of FFB from MDS in the water medium decreased with an increasing percentage of S(mix) added to both water contents. However, the release rates and amounts of FFB from MDSs increased with an increasing percentage of S(mix) in a 0.025 M sodium lauryl sulfate (SLS) solution. It was further illustrated that the release of FFB from SMEDDSs was complete within 30 min in both the 0.025 M SLS solution and water medium, but the release of FFB from Tricor® or MDSs was limited in water medium. An optimised FFB SMEDDS with either Tween 20(E5(20)) or Tween 80(E5(80)) and one MDS were selected for a pharmacokinetic study to compare with Tricor(®). The results demonstrated that the area under the receiver operating curve and C(max) values were in the order of Tricor(®) > E5(80)≅E5(20) > MDS and Tricor(®)≅E5(80) > E5(20) > MDS, respectively. Conclusions The absorption of drug carried by SMEDDS might not be enhanced as a result of the smaller volume of water taken with oral administration of SMEDDSs and the agitation rate of the gastrointestinal tract not being strong enough to efficiently promote the self-microemulsification process to facilitate the in-vivo dissolution rate.

Assessing the performance of amorphous solid dispersions

“…Although stirring rate is an important factor in dissolution testing, it is suggested that investigations related to mixing and agitation rates encountered in vivo also be conducted. [90][91][92][93][94][95][96] …”

“…Furthermore, churning and agitation will differ based on the fed and fasted states; therefore, a closer inspection of the dissolution apparatus speeds and a better assessment of the agitation on dissolution also needs to be considered. [91][92][93][94][95][96] The presence of food will change the pH in the stomach; however, the changes are not uniform throughout the three distinct regions of the stomach (fundus, body, and antrum). 101,102 It was revealed that the gastric body and fundal pHs raised to a pH 4.5 in a time-dependent manner postfeeding, 101 whereas the antral pH remained at 2 throughout the time that food was present.…”

“…Dissolution methods to better mimic in vivo factors such as mixing and agitation due to the muscle layers have also been developed and need to be considered for routine use. [91][92][93][94][95][96] The presence of a high amount of polymer in solid amorphous dispersions can also play an important role in designing the dissolution experiment. Many polymers have very different properties compared with APIs and excipients and these need to be incorporated into the method development.…”

“…98,126 Changes along the GI tracts of the rats and dogs appeared to vary more when compared with human values, whereas the pig, another nonprimate species increasingly being used in safety pharmacology studies, was more similar to humans. [91][92][93][94][95][96][97]124 Monkeys actually had higher variability than any other species when compared with humans, with stomach pH ranges of 4.7-5.0 being normal. 124 This is important when considering the effects that can occur with weak acids and weak bases during development.…”

Effect of Lipolysis on Drug Release from Self-microemulsifying Drug Delivery Systems (SMEDDS) with Different Core/Shell Drug Location

“…Many studies have demonstrated that enhanced drug release from SMEDDS could improve the bioavailability (6,(10)(11)(12)(13)(14)(15). However, SMEDDS is digestible and undergoes complicated structural changes in the gastrointestinal tract.…”