Preparation and characterization of 9-nitrocamptothecin self-emulsifying microemulsion injection

Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.

In vitro Dissolution and Pharmacokinetics in Beagle Dogs of a Self-Emulsifying Formulation of Tretinoin

Aim In vitro dissolution test and pharmacokinetics in beagle dogs wereconducted to assess the formulation of tretinoin in self-emulsifying systems. Methods Theconcentrations of tretinoin were determined by HPLC. A crossover study was performed in four fastingbeagle dogs with the formulation of self-emulsifying systems and commercial capsules. Results Theresults showed that the dissolution rate in 15 min of tretinoin in self-emulsifying systems washigher than 80% while that of the commercial capsules was lower than 5% . The area under the plasmaconcentration-time curve (AUC) of the self-emulsifying formulation was significantly higher andC_(max) was approximately two times greater than those of commercial capsule, respectively, Inaddition, the time taken to reach peak was shorter (2 h to 1.25 h) for self-emulsifying formulationof tretinoin. Conclusion The self-emulsifying drug delivery systems.can significantly increasetretinoin in vitro dissolution and in vivo absorption.

Preparation and evaluation of alpha-mangostin solid self-emulsifying drug delivery system

Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory[1].However,it has poor aqueous-solubility and dissolution,which results in low bioavailability.Solid self-emulsifying drug delivery system(solid-SEDDS),an effective pharmaceutical strategy,offers the potential for enhancing the oral bioavailability of poorly water-soluble drugs[2].Therefore,solid-SEDDS is of interest as a potential method for enhancing the solubility and dissolution of AMG.

A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution

To enhance the dissolution of poorly soluble mefenamic acid,self-emulsifying formulation(SEF),composing of oil,surfactant and co-surfactant,was formulated.Among the oils and surfactants studied,Imwitor■ 742,Tween■ 60,Cremophore■ EL and Transcutol■ HP were selected as they showed maximal solubility to mefenamic acid.The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading.The droplet size after dispersion and drug dissolution of selected formulations were investigated.The results showed that the formulation containing Imwitor■ 742,Tween■ 60 and Transcutol■ HP(10:30:60)can encapsulate high amount of mefenamic acid.The dissolution study demonstrated that,in the medium containing surfactant,nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min.In phosphate buffer(without surfactant),80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min,from the commercial product.The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.

Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides

Orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and convenience.However,the development of oral protein formulations has stalled due to the low bioavailability of macromolecules that encounter the aggressive gastrointestinal environment and harsh mucus villi barrier.Herein,we propose an ideal reverse micelle/self-emulsifying drug delivery system(RM/SEDDS)nanoplatform that is capable of improving the oral bioavailability of hydrophilic peptides by preventing enzymatic degradation and enhancing mucosal permeability.Upon the passage through the mucus,the self-emulsifying drug delivery system with optimal surface properties effectively penetrates the viscoelastic mucosal barrier,followed by the exposure of the inner reverse micelle amphipathic vectors,which autonomously form continua with the lipidic cell membrane and facilitate the internalization of drugs.This membrane-fusion mechanism inaugurates a new way for hydrophilic peptide delivery in the free form,circumventing the traditional impediments of the cellular internalization of nanocarriers and subsequent poor release of drugs.And more importantly,reverse micelles are not spatially specific to the laden drugs,which enables their delivery for a myriad of peptide clinical drugs.In conclusion,as an exquisitely designed nanoplatform,RM/SEDDS overcomes multiple physiological barriers and opens a new path for drug cellular entry,providing new prospects for the development of oral drug delivery systems.

Insoluble drug delivery strategies: review of recent advances and business prospects

The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve ef fi cacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies.This review covers the recent advances in the fi eld of insoluble drug delivery and business prospects.

Integrated in silico formulation design of selfemulsifying drug delivery systems

The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods.Random forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation.The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of oil-surfactant-cosurfactant.Finally,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of cosurfactants.In conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation design.The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

Formulation optimization, in situ intestinal absorption and permeability of psoralen and isopsoralen

Objective: To optimize a self-emulsifying drug delivery system(SEDDS) formulation for psoralen and isopsoralen(PSO and IPSO) isolated from Psoraleae Fructus.Methods: A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity,equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system.Results: The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be53.6%, 35.7% and 10.7%, respectively, which means the model is available.Conclusions: The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.