Formulation in vitro and in vivo evaluation of SRMS-based heterolipid-templated homolipid delivery system for diclofenac sodium

Abstract

The sole objective of this work was to design successful dosage oral forms of diclofenac sodium (DiNa)-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS). Hot homogenization technique was employed to prepare DicNa SLM using a mixture goat fat and Phospholipon® 90 G as lipid matrix and Tween®-80 as mobile surfactant. Characterization based on percentage yield, morphology, particle size, zeta potential, percentage encapsulation, pH and stability of SLMs were investigated. Anti-inflammatory, gastrointestinal tract (GIT) sparing effect and pharmacokinetics were carried out in rat model after oral administration. Results showed that the SLMs were spherical and smooth. The optimized formulation (SLM-4) had particle size of 79.40 ± 0.31 µm, polydispersity index of 0.633 ± 0.190, zeta potential of -63.20 ± 0.12 mV and encapsulation efficiency of 91.2 ± 0.1% with good stability after 8 months of storage. The DicNa SLM had sustained release effect with good anti-inflammatory activity. Higher and prolonged plasma DicNa concentration was shown by the SLM-4 compared to pure drug and a conventional sample. These studies demonstrate that DicNa-loaded SLM based on SRMS could be a promising oral formulation for enhanced bioavailability, pharmacologic activity and gastrointestinal sparing effect of the NSAID, DicNa.

<p>Comparative Encapsulation Efficiency of Lutein in Micelles Synthesized via Batch and High Throughput Methods</p>

“… 34 , 35 These materials were chosen for their biocompatibility, established characterization techniques, enhanced encapsulation abilities, and sustained release dynamics. 29 As a comparison, we also analyzed PHOSPHOLIPON 90G (P90G), which has been previously used for oral delivery of poorly soluble compounds in preclinical studies, 36–38 but which has not previously been employed in scalable processes. P90G is an FDA-approved, commercially-available, amphiphilic lipid (unsaturated diacyl-phosphatidylcholine) derived from soybean fatty acids ( Figure 2 ).…”

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

“…We are curious to know the role of this potential molecule in the pharmacokinetics and consequent efficacy of diclofenac in the form of a suitable pharmaceutical composition. There are a quite a few reports in the literature which underline the importance of improvement in oral bioavailability/efficacy of diclofenac in modern treatment (Assali, Shawahna, Dayyeh, Shareef, & Alhimony, ; Cooper, Wood, Wyatt, & Harirforoosh, ; Mumuni, Attama, & Kunle, ).…”

Fatty Acid Esters of G0-(Propyl Ether Imine) Dendron as Bicephalous Heterolipids for Permeation Enhancement in Transdermal Drug Delivery

“…Several types of chemical compounds including azones, glycols, sulfoxides, fatty acid esters, surfactants, lipids, and polymers are investigated as CPEs. However, many of these compounds are not safe for human use and show significant dermal irritation and other adverse effects. , To address the safety issues, many semisynthetic lipids, natural oils, and polymer–lipids hybrids are investigated as potential CPEs with emphasis on selection of biomaterials native to human metabolic systems or their closely related derivatives. ,,,,− …”

“…A large number of lipids are available; however, selection of the right candidate from the pool of lipids for chemical permeation enhancement relies on trial and error methods and is very tedious and time-consuming. It would be simpler and more rational if along with developing a pool of new lipidic materials information on their structure–property relationship was also investigated and made available. − Recently, fatty acid derivatives, dendrimer–lipid hybrids, and heterolipids have been investigated as CPEs and were found to be effective as skin permeation enhancers for drugs such as diclofenac sodium (DS), having poor skin permiability. − Heterolipids are complex lipids containing N and P atoms in addition to the usual C, H, and O. The trivalent nitrogen atom incorporated in the chemical structure provides scope as a branching element, on which structural diversities can be constructed to attain property diversity as well as impart basic properties to the lipids.…”

“…Our research group is actively engaged in synthesis and development of new heterolipids for drug delivery applications. − , We have synthesized a few heterolipids such as novel janus type oleodendrimers and demonstrated their effectiveness as CPEs using diclofenac sodium (DS), a nonsteroidal anti-inflammatory agent, as a model drug. − With the success of oleodendrimers as effective CPEs, further work was undertaken to synthesize a pool of heterolipids and investigate the effect of their chemical structure on skin permeation enhancement …”