Types Of Lipid-based Formulations Research Articles

In Vitro Digestion-In Situ Absorption Setup Employing a Physiologically Relevant Value of the Membrane Surface Area/Volume Ratio for Evaluating Performance of Lipid-Based Formulations: A Comparative Study with an In Vitro Digestion-Permeation Model.

The aim of this study is to establish and test an in vitro digestion-in situ absorption model that can mimic in vivo drug flux by employing a physiologically relevant value of the membrane surface area (S)/volume (V) ratio for accurate prediction of oral drug absorption from lipid-based formulations (LBFs). Three different types of LBFs (Type IIIA-MC, Type IIIA-LC, and Type IV) loaded with cinnarizine (CNZ), a lipophilic weak base with borderline permeability, and a control suspension were prepared. Subsequently, a simultaneous in vitro digestion-permeation experiment was conducted using a side-by-side diffusion cell with a dialysis membrane having a low S/V value. During digestion, CNZ partially precipitated for Type IV, while it remained solubilized in the aqueous phase for Type IIIA-MC and Type IIIA-LC in the donor compartment. However, in vitro drug fluxes for Type IIIA-MC and Type IIIA-LC were lower than those for Type IV due to the reduced free fraction of CNZ in the donor compartment. In pharmacokinetic studies, a similar improvement in in vivo oral exposure relative to suspension was observed, regardless of the LBFs used. Consequently, a poor correlation was found between in vitro permeation and areas under the plasma concentration-time curve (AUCoral) (R2 = 0.087). A luminal concentration measurement study revealed that this discrepancy was attributed to the extremely high absorption rate of CNZ in the gastrointestinal tract compared to that across a dialysis membrane evaluated by the in vitro digestion-permeation model, i.e., the absorption of CNZ in vivo was completed regardless of the extent of the free fraction, owing to the rapid removal of CNZ from the intestine. Subsequently, we aimed to predict the oral absorption of CNZ from the same formulations using a model that demonstrated high drug flux by employing the physiologically relevant S/V value and rat jejunum segment as an absorption sink (for replicating in vivo intestinal permeability). Predigested formulations were injected into the rat intestinal loop, and AUCloop values were calculated from the plasma concentration-time profiles. A better correlation was found between AUCloop and AUCoral (R2 = 0.72), although AUCloop underestimated AUCoral for Type IV due to the precipitation of CNZ during the predigestion process. However, this result indicated the importance of mimicking the in vivo drug absorption rate in the predictive model. The method presented herein is valuable for the development of LBFs.

The impact of quantity of lipid based formulations with different compositions on the oral absorption of ritonavir: A trade-off between apparent solubility and permeability

In this study, the effect of the quantity of lipid-based formulations (LBFs) on the oral absorption of ritonavir (RTV), a model for poorly water-soluble drugs, was investigated. Two types of LBFs, comprising short- and medium-chain lipids (LBF-SMC) and long-chain lipids (LBF-LC) loaded with different masses of RTV, were prepared. Then, the respective LBFs were dispersed in distilled water at concentrations of 1.0, 2.0, and 3.0% w/w, which provided the same drug concentration for all formulations. When 1.0% LBF-SMC and LBF-LC were orally administered to rats, the oral absorption was significantly improved compared with that of the suspension (a reference formulation) because of enhanced solubilization of RTV in the gastrointestinal tract; however, this improvement was lower for LBF-LC than for LBF-SMC. The oral absorption decreased with increasing LBF concentration for both LBF-SMC and LBF-LC. The in vitro permeation in sequence with in vitro digestion revealed that this phenomenon was caused by a reduction in the free drug concentration in the gastrointestinal tract. Moreover, the effect of decreasing the free concentration was more remarkable for LBF-LC than for LBF-SMC because of the greater solubilization capacity of LC digestion products. These findings may be useful for designing improved drug delivery systems.

Transdermal Delivery of Macromolecules Using Nano Lipid Carriers.

Skin being the largest external organ, offers an appealing procedure for transdermal drug delivery, so the drug needs to reach above the outermost layer of the skin, i.e., stratum corneum. Small molecular drug entities obeying the Lipinski rule, i.e., drugs having a molecular weight less than 500 Da, high lipophilicity, and optimum polarity, are favored enough to be used on the skin as therapeutics. Skin's barrier properties prevent the transport of macromolecules at pre-determined therapeutic rates. Notable advancements in macromolecules' transdermal delivery have occurred in recent years. Scientists have opted for liposomes, the use of electroporation, low-frequency ultrasound techniques, etc. Some of these have shown better delivery of macromolecules at clinically beneficial rates. These physical technologies involve complex mechanisms, which may irreversibly incur skin damage. Majorly, two types of lipid-based formulations, including Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs), are widely investigated as transdermal delivery systems. In this review, the concepts, mechanisms, and applications of nanostructured lipid carriers used to transport macromolecules via transdermal routes are thoroughly reviewed and presented along with their clinical perspective.

Improving oral bioavailability of medicinal herbal compounds through lipid-based formulations – A Scoping Review

BackgroundAlthough numerous medicinal herbal compounds demonstrate promising therapeutic potential, their clinical application is often limited by their poor oral bioavailability. To circumvent this barrier, various lipid-based herbal formulations have been developed and trialled with promising experimental results. PurposeThis scoping review aims to describe the effect of lipid-based formulations on the oral bioavailability of herbal compounds. MethodsA systematic search was conducted across three electronic databases (Medline, Embase and Cochrane Library) between January 2010 and January 2021 to identify relevant studies. The articles were rigorously screened for eligibility. Data from eligible studies were then extracted and collated for synthesis and descriptive analysis using Covidence. ResultsA total of 109 studies were included in the present review: 105 animal studies and four clinical trials. Among the formulations investigated, 50% were emulsions, 34% lipid particulate systems, 12% vesicular systems, and 4% were other types of lipid-based formulations. Within the emulsion system classification, self-emulsifying drug delivery systems were observed to produce the best improvements in oral bioavailability, followed by mixed micellar formulations. The introduction of composite lipid-based formulations and the use of uncommon surfactants such as sodium oleate in emulsion preparation was shown to consistently enhance the bioavailability of herbal compounds with poor oral absorption. Interestingly, the lipid-based formulations of magnesium lithospermate B and Pulsatilla chinensis produced an absolute bioavailability greater than 100% indicating the possibility of prolonged systemic circulation. With respect to chemical conjugation, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was the most frequently used and significantly improved the bioavailability of its phytoconstituents. ConclusionOur findings suggest that there is no distinct lipid-based formulation superior to the other. Bioavailability improvements were largely dependent on the nature of the phytoconstituents. This scoping review, however, provided a detailed summary of the most up-to-date evidence on phytoconstituents formulated into lipid preparations and their oral bioavailability. We conclude that a systematic review and meta-analysis between bioavailability improvements of individual phytoconstituents (such as kaempferol, morin and myricetin) in various lipid-based formulations will provide a more detailed association. Such a review will be highly beneficial for both researchers and herbal manufacturers.

Effects of Lipid Digestion and Drug Permeation/Re-Dissolution on Absorption of Orally Administered Ritonavir as Different Lipid-Based Formulations

The aim of this study is to clarify absorption mechanisms after oral administration of ritonavir (RTV) from different types of lipid-based formulations (LBFs) with particular emphasis on the effect of lipid digestion and drug permeation/re-dissolution on the oral absorption. Four LBFs were prepared; three contained either long-chain (LC) or medium-chain (MC) lipids [lipid formulation classification system (LFCS) Type II-LC, Type IIIA-MC, and Type IIIB-MC] and the fourth contained only surfactant and co-solvent (Type IV). The solubility of RTV in those LBFs was determined and drug subsequently loaded at 85% w/w of the saturated solubility in the formulations. Then, each LBF containing drug was added into a model rat intestinal fluid at approximately 2.5% w/v for evaluation using an in vitro digestion model. In vitro digestion study showed the ability of Type II-LC and Type IIIA-MC to support continued solubilization of RTV, and moderate supersaturation was observed in Type IIIA-MC. In contrast, RTV partly precipitated in the Type IIIB-MC during digestion, and the Type IV formulation lost its solubilization capacity rapidly upon dispersion, leading to drastic precipitation. Oral administration of RTV as Type IIIA-MC to rats showed significantly higher area under the plasma concentration-time curve compared to control suspension, whereas it was not improved with Type II-LC administration despite complete solubilization of RTV during digestion. From the results of in vitro permeation across dialysis membrane (a molecular weight cutoff of > 1000 Da), this may be attributed to the lowered free concentration in the gastrointestinal tract owing to incorporation of RTV into the undigested LC lipid. Oral absorption drastically increased with Type IIIB-MC and Type IV despite the observed moderate and drastic precipitation, respectively. Powder X-ray diffraction analysis revealed that the precipitate was amorphous. Therefore, improved re-solubilization may partly contribute to improved absorption. The present study revealed detailed absorption mechanisms from LBFs with different compositions. Our findings may be useful for selecting appropriate excipients to design optimal LBFs for poorly water-soluble drugs.

Control of oral absorption of nutritional supplement using lipid-based formulations (LBFs): Application to the poorly water-soluble ingredient

Among various formulations for oral use, lipid-based formulation (LBF) has been expected as a promising technology to improve the absorption of poorly water-soluble compounds. In the current study, three types of LBFs were tested for their effects on the extent, rate and variability of oral absorption of sesamin. Olive oil (type 1), type 3A-MC (medium-chain lipids) and type 3A-LC (long-chain lipids) formulations were prepared to test the intestinal absorption of sesamin in rats. Both type 3A formulations showed a rapid absorption of sesamin with minimized inter-individual variability compared to Olive oil formulation. Extent of absorption was in the order of 3A-LC > Olive oil > 3A-MC ≫ powder suspension. It was revealed that 3A-LC formulation kept the high solubilization capacity even under the lipid-digestive condition giving a high concentration of free sesamin. In the dog study, 3A-LC formulation also showed a high and less-variable absorption of sesamin, although the absorption was subjected to the effect of food intake. In conclusion, the extent, rate and variability of oral absorption of sesamin could be controlled by using different types of LBFs, indicating the possibility to develop better oral products of supplements using appropriate formulations.