Biorelevant Media Research Articles

Evaluation of the impact of age-specific bile salt differences on the dissolution behavior of voriconazole using biorelevant media

Evaluation of the impact of age-specific bile salt differences on the dissolution behavior of voriconazole using biorelevant media

Evaluation of the impact of age-specific bile salt differences on the dissolution behavior of voriconazole using biorelevant media

Evaluation of the impact of age-specific bile salt differences on the dissolution behavior of voriconazole using biorelevant media

Determination of dissolution rate of prolonged-release tablets in bio-relevant media using USP apparatus III

Determination of dissolution rate of prolonged-release tablets in bio-relevant media using USP apparatus III

Biorelevant Dissolution Method Considerations for the Appropriate Evaluation of Amorphous Solid Dispersions: are Two Stages Necessary?

Biorelevant dissolution testing has been widely used to better understand a drug or formulation's behavior in the human gastrointestinal (GI) tract. The successful evaluation of biorelevant dissolution behavior requires recognizing the importance of utilizing suitable biorelevant media in conjunction with an appropriate dissolution method, especially for supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs). However, most conventional biorelevant dissolution testing methods are not able to accurately reflect the dissolution, supersaturation, and precipitation tendencies of a drug or formulation, which could misinform ASD formulation screening and optimization. In this study, we developed a single compartment 2-stage pH-shift dissolution testing method to simulate the changes in pH, media composition, and transit time in the GI tract, and results were compared against the conventional single compartment 1-stage dissolution method. Nine model drugs were selected based on their ionization properties (i.e. acid, base or neutral) and precipitation tendency (i.e. moderate or slow crystallizer). The dissolution results confirmed that 2-stage pH-shift dissolution is the preferred biorelevant dissolution method to assess non-ionized weak base (nifedipine) and neutral (griseofulvin) compounds exhibiting a moderate precipitation rate from solution when formulated as ASDs. Finally, we designed a flowchart guidance for the appropriate biorelevant dissolution performance characterization of different categories of ASD formulations.

Oral delivery of calcitonin-ion pairs: In vivo proof of concept for a highly lipophilic counterion

Hydrophobic ion pairing and subsequent incorporation into self-emulsifying drug delivery systems (SEDDS) is a promising strategy to orally deliver hydrophilic macromolecular drugs. Within this study, hydrophobic ion pairs (HIP) between salmon calcitonin (sCT) and highly lipophilic sulfosuccinate counterions were formed and compared to frequently applied commercially available counterions. Bis(isotridecyl) sulfosuccinate resulted in HIPs of the highest lipophilicity and in significantly higher solubility in lipophilic co-solvents. Thus, bis(isotridecyl) sulfosuccinate allowed efficient solubilization of sCT in a SEDDS preconcentrate based on a lipophilic co-solvent and an indigestible lipid, but omitting hydrophilic co-solvents. In addition to the increased solubility in the lipidic matrix, markedly reduced dissociation in biorelevant media resulted in high distribution coefficients between oil droplet and FaSSGF or FaSSIF (logD) of 2.98 ± 0.12 or 2.77 ± 0.14, respectively. The composition of the lipidic matrix preserved integrity of the oil droplets after emulsification and subsequent lipolysis, allowing to fully exploit the potential of the HIP attributed to the high logD. Oral administration of the HIP-loaded SEDDS resulted in an excellent relative pharmacological activity of 13.8 ± 5.6 % measured as hypocalcaemic effect in rats.

Interaction of polymers with bile salts – Impact on solubilisation and absorption of poorly water-soluble drugs

Formulating poorly soluble drugs with polymers in the form of solid dispersions has been widely used for improving drug dissolution. Endogenous surface-active species present in the gut, such as bile salts, lecithin and other phospholipids, have been shown to play a key role in facilitating lipids and poorly soluble drugs solubilisation in the gut. In this study, we examined the possible occurrence of interactions between a model bile salt, sodium taurocholate (NaTC), and model spray dried solid dispersions comprising piroxicam and Hydroxypropyl Methylcellulose (HPMC), a commonly used hydrophilic polymer for solid dispersion preparation. Solubility measurements revealed the good solubilisation effect of NaTC on the crystalline drug, which was enhanced by the addition of HPMC, and further boosted by the drug formulation into solid dispersion. The colloidal behaviour of the solid dispersions upon dissolution in biorelevant media, with and without NaTC, revealed the formation of NaTC-HPMC complexes and other mixed colloidal species. Cellular level drug absorption studies obtained using Caco-2 monolayers confirmed that the combination of drug being delivered by solid dispersion and the presence of bile salt and lecithin significantly contributed to the improved drug absorption. Together with the role of NaTC-HPMC complexes in assisting the drug solubilisation, our results also highlight the complex interplay between bile salts, excipients and drug absorption.

A Simple One-Parameter Percent Dissolved Versus Time Dissolution Equation that Accommodates Sink and Non-sink Conditions via Drug Solubility and Dissolution Volume

In vitro dissolution generally involves sink conditions, so dissolution equations generally do not need to accommodate non-sink conditions. Greater use of biorelevant media, which are typically less able to provide sink conditions than pharmaceutical surfactants, necessitates equations that accommodate non-sink conditions. One objective was to derive an integrated, one-parameter dissolution equation for percent dissolved versus time that accommodates non-sink effects via drug solubility and dissolution volume parameters, including incomplete solubility. A second objective was to characterize the novel equation by fitting it to biorelevant dissolution profiles of tablets of two poorly water-soluble drugs, as well as by conducting simulations of the effect of dose on dissolution profile. The Polli dissolution equation was derived, % ;dissolved=100%left[1-frac{left({{M}_{0}-c}_{s}Vright)}{{M}_{0}-{{c}_{s}Ve}^{{-k}_{d}left(frac{{{M}_{0}-c}_{s}V}{V}right)t}}right], where M0 is the drug dose (mg), cs is drug solubility (mg/ml), V is dissolution volume (ml), and kd is dissolution rate coefficient (ml/mg per min). Maximum allowable percent dissolved was determined by drug solubility and not a fitted extent of dissolution parameter. The equation fit tablet profiles in the presence and absence of sink conditions, using a single fitted parameter, kd, and where solubility ranged over a 1000-fold range. kd was generally smaller when cs was larger. FeSSGF provided relatively small kd values, reflecting FeSSGF colloids are large and slowly diffusing. Simulations showed impact of non-sink conditions, as well as plausible kd values for various cs scenarios, in agreement with observed kd values. The equation has advantages over first-order and z-factor dissolution rate equations. An Excel file for regression is provided.Graphical

Insights into the Role of Compendial/Biorelevant Media on the Supersaturation Behaviour of Drug Combination (Drug-Drug Interaction) and Precipitation Inhibition by Polymers.

Combination drug therapy (CDT) plays an immense role in the treatment of various diseases such as malaria, hypertension, cancer, HIV-AIDS, helminthiasis, and many more. However, in vitro drug-drug interaction (DDI) is not well reported for better efficacy of CDT. In DDI one drug may enhance the precipitation of other drugs thereby reducing the advantage of CDT. Herein, we report DDI in terms of in vitro precipitation of drugs with albendazole and mebendazole. This may be the first report to propensate the possibility of either drug precipitation in the combination. These drugs are categorized into BCS class II weak base and hence have tendency to precipitate in the gastrointestinal tract. The objective of this study is to find precipitation of drug combinations in different compendial and biorelevant media (deionized water, phosphate buffer pH 6.8, FaSSIF, and FeSSIF) and screening of the polymers for precipitation inhibition. Nine polymers were investigated at three different concentrations in terms of their drug-polymer solubility, in vitro precipitation behavior, induction time, SHC, and droplet size. Although, all the polymers inhibit the precipitation of drugs, the extent of precipitation inhibition for Soluplus is high. The obtained drug-polymer precipitates were filtered, dried, and analyzed for amorphous/partial amorphous form using polarised light microscopy (PLM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). The drug-polymer interaction was examined using Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) revealing the effect of polymers on drug precipitation. These insights may further be used in the formulation of CDT for helminthiasis management.

Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution.

Praziquantel is a poorly water-soluble drug used to treat parasitic infections. Previous studies have suggested that its rate and extent of dissolution in milk and biorelevant media are slow and limited compared to dissolution in the pharmacopoeial-recommended medium, despite being reported as displaying a positive food effect upon administration. This study aimed to revisit the dissolution of praziquantel in biorelevant media and milk to better understand this apparent dichotomy. The context of digestion was introduced to better understand drug solubilisation under more relevant gastrointestinal conditions. The amount of praziquantel solubilised in the various media during digestion was quantified using high performance liquid chromatography (HPLC) and the kinetics of dissolution were confirmed by tracking the disappearance of solid crystalline drug using in situ small angle X-ray scattering (SAXS). For the dissolution media, where sodium lauryl sulfate (SLS) is typically included as a wetting agent, a prominent effect of SLS on drug dissolution was also apparent where >2.5 fold more drug was solubilised in SLS-containing dissolution medium compared to that without (0.1 M HCl only). In milk, significant dissolution of praziquantel was observed only during digestion and not during dispersion, hence suggesting that (1) milk can be potentially administered with praziquantel to improve oral bioavailability and (2) incorporating a digestion step into existing in vitro dissolution testing can better reflect the potential for a positive food effect when lipids are present.

Should the Use of Acid Reducing Agents in Conjunction with Ribociclib be Avoided? An Integrated QbD Approach for Assessment of pH-Mediated Interaction.

The objective of the study was to evaluate the possible pH-dependent interaction of ribociclib succinate with acid-reducing agents, which are concomitantly administered as supportive care medicines in cancer. Quality by Design-based analytical method development for a weakly basic drug ribociclib succinate supposedly having the characteristic ability of pH-dependent solubility was carried out for analyzing micro-dissolution experiment samples in biorelevant media to study pH-dependent interaction. An accurate and robust analytical method was developed using a three-level three-factorial box-behnken design for quantification of ribociclib succinate in micro-dissolution samples by the implementation of the Analytical Quality by Design approach. Here, pH of aqueous mobile phase and flow rate proved to be critical process parameters. The gastric compartment solubility was found to be 814.05μg/mL, which dropped down to 494.71μg/mL after a pH shift from pH1.2-6.5. In the intestinal compartment, initial solubility was 717.58μg/mL, which reduced to 463.20μg/mL after a pH shift from 6.5 to 6.8. Concluded results state that pH shift does not impact the solubility or the absorption of the drug to a significant extent in the presence of acid-reducing agents. However, the study would prove to be a practical approach for examination of the behavior of the drugs at the initial stages.

Pharmaceutical Product Characterization and Manufacturability of Surfactant-Enriched Oil Marbles with Abiraterone Acetate.

The present study investigates the physicochemical properties and stability of a novel lipid-based formulation-surfactant-enriched oil marbles containing abiraterone acetate. While the biopharmaceutical performance of this formulation has been reported recently, this study aims to fill the gap between a promising in vivo performance and industrial applicability. A series of techniques were employed to assess the solid-state characteristics of oil marble cores along with their physicochemical properties upon stability testing. The chemical stability of abiraterone acetate in the formulation was also investigated. The core of the formulation was found to be stable both physically and chemically over 12months of storage. The in vitro performance of stressed samples was evaluated using a dissolution experiment. The formulation has successfully self-emulsified upon incubation in bio-relevant media, resulting in a fast and complete API release. An important issue connected with the excipient used as a covering material of oil marbles has been identified. The seemingly insignificant water sorption caused agglomeration of the oil marbles and consequently compromised the dissolution rate in some of the stressed samples. Replacing HPMC with lactose as a covering material resulted in more favorable properties upon storage. Overall, it has been shown that oil marbles are an industrially applicable concept of the solidified lipid-based formulation.

Evaluation of pH Dependent Solubility and Examination of Variation in Pharmacokinetic Properties of Alectinib: A Quantitative Study by Implementing Integrated Quality by Design Approach for RP-HPLC Method Development and Optimization

Abstract: Introduction: Alectinib, an anaplastic lymphoma kinase inhibitor of BCS class IV, is said to have pH-dependent solubility and is susceptible to interactions with co-prescribed acid-reducing agents. Objectives: A micro-dissolution study was performed to determine the effect of modulations in gastrointestinal pH using biorelevant media and a sensitive RP-HPLC technique was developed for quantification of alectinib in the same using quality by design approach. Materials and Methods: Analytical method was developed and optimized in accordance with box-behnken design followed by micro-dissolution experiment mimicking physiological pH shift. Results: The solubility of alectinib in FaSSGF decreased from 0.648 μg/ml to 0.270 μg/ml whereas in FaSSIF it dropped down from 0.574 μg/ml to 0.108 μg/ml at the end of the micro-dissolution experiment. This reveals that elevation of pH from 1.2 to 6.8 has no significant impact on its solubility and hence will not influence drug absorption. Conclusion: Nonetheless, the study would be useful for therapeutic medication monitoring, dose adjustment of co-administered drugs, proactively driving clinical research design, and obtaining a readout on pH liability for high-risk anticancer medications. Keywords: Alectinib, QbD, pH, ALK kinase, Micro dissolution.

Quantitative assessment of disintegration rate is important for predicting the oral absorption of solid dosage forms containing poorly soluble weak base drugs

This study aimed to develop a novel in silico modeling and simulation that considers the disintegration rate in the stomach to predict the in vivo performance of oral solid dosage forms with slow disintegration rates containing poorly soluble weak base drugs. Oxatomide and manidipine hydrochloride were used as model drugs. First, the in vitro disintegration rate and dissolution rate were determined in biorelevant media that simulate the gastrointestinal fluids in fasted humans using a USP apparatus II paddle dissolution tester. Next, the oral absorption of the dosage forms was predicted using the novel simulation model coupled with not only the dissolution rate but also the estimated disintegration rate. As the in vitro disintegration time was 45 min or longer for both drugs in Fasted State Simulated Gastric Fluid, the disintegration rate of these dosage forms was considered slow as immediate release (IR) tablets. While the predicted and observed pharmacokinetic profiles of both drugs were comparable using the new model, the conventional model, which did not consider the disintegration step, underestimated the oral absorption of both drugs. Thus, our novel simulation model coupled with the disintegration rate estimated from in vitro tests is promising for predicting the in vivo performance of oral solid dosage forms with slow disintegration rates containing poorly soluble weak base drugs.

Solution Stability of Pharmaceutical Cocrystals

In recent years, pharmaceutical cocrystals as a new solid form have received considerable attention among the applied novel methods for modifying drug substance characteristics. Crystal engineering offers an excellent opportunity to improve physicochemical and pharmacokinetic properties such as solubility, dissolution rate, permeability, bioavailability, biochemical/physical stability, etc. Application of the cocrystal form in the pharmaceutical industry and in academia is becoming a popular method to overcome solubility disadvantages of the active pharmaceutical ingredient (API). Due to manipulation of the API crystalline structure by cocrystal formation, solubility is not the only affected property; some other properties of the newly produced solid form must be considered to fulfill the desired therapeutic efficacy. The stability of the cocrystal in solution is one of these influential features. Regarding the aqueous nature of the gastrointestinal tract, unwanted solution-mediated phase transformation of a cocrystal to a more stable form causes inefficient drug delivery. It may potentially reduce the drug concentration in the circulation. Cocrystal transformation products could be a different polymorph, hydrated form, or mixture of the API and coformer. This review focuses on the solution stability of cocrystals and the effects of various factors such as polymers, surfactants, biorelevant media, organic solvents, and pH.

A simple and green liquid chromatography method for the determination of ibuprofen in milk-containing simulated gastrointestinal media for monitoring the dissolution studies of three-dimensional-printed formulations.

A fast and green ultra-high-performance liquid chromatographic method was developed for the determination of ibuprofen in milk-containing simulated gastrointestinal media to monitor the dissolution of three-dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The β-expectation tolerance intervals did not exceed the acceptance criteria of±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01μg/ml and the lower limit of quantitation was established as 2μg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.

In- vitro biorelevant media and time simulation probiotic proliferation methodology to determine prebiotic potentials of flaxseed powder

Dysbiosis is defined as disorganization of microflora homeostasis, leading to changes in metabolic activities and local distribution with major impacts on functional composition. Presently, gut microbiota modifications, with the objective to treat microbial dysbiosis, is well known treatment option preferred for conditions involving gut flora disturbances. It has been found that the most common approach to treat gut flora disturbance is to prescribe probiotic supplements. The objective of the present research was to develop simple methodology in order to determine the prebiotic potential of flaxseed powder using a novel in-vitro bio-relevant media and a time simulation proliferation approach for the marketed probiotic Bacillus coagulans SNZ 1969, (“Sporlac Sachets, Sanzyme Biologics Private Limited”). In addition to the desired result, the current study also yielded pertinent information on fermented flaxseed powder and helpful data regarding prescription guidelines for commercially available probiotic supplements. It has been observed that various factors like gastrointestinal pH, transit time, gastrointestinal fluid composition, presence of prebiotics, and fermentation play an important role in the proliferation and gastrointestinal colonization of orally ingested probiotics. The research findings justify the importance of synbiotic and postbiotics supplement approaches as the part of treatment and prescription requirements in gut flora microbial dysbiosis rather than probiotic supplements alone. Alternatively, patients could be guided for the concept that the consumption of prebiotic-containing foods have potential to enhance the ability of probiotics to restore the gut flora following a course of antibiotic therapy.

A β-Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer.

β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β–sitosterol encapsulated Alginate/Chitosan nanoparticles (β–sito–Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β–sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β–sito–Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β–sito–Alg/Ch/NPs as compared to β–sito–suspension. The β–sito–Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β–sito–Alg/Ch/NPs and β–sito–suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β–sito–Alg/Ch/NPs and β–sito–suspension. When compared to the β–sito–suspension, the β–sito–Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β–sito–Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β–sito–suspension.

Prediction of food effect on in vitro drug dissolution into biorelevant media: Contributions of solubility enhancement and relatively low colloid diffusivity

A prior model that showed good predictability for fed-state and fasted-state biorelevant media was extended to predict the degree to which fed-state biorelevant media (i.e. FeSSGF and FeSSIF-V2) enhanced drug dissolution over fasted-state biorelevant media (i.e. FaSSGF and FaSSIF-V2): ϕfood=vfast1/6vfed1/6·(ff,fedDD2/3+fm,fedDD−M,fed2/3)[Dt,fed](ff,fastDD2/3+fm,fastDD−M,fast2/3)[Dt,fast] where ϕfood is the degree by which fed-state biorelevant media enhanced in vitro drug dissolution over fasted state biorelevant media, ff,fast and ff,fed are the fraction of free drug in fasted and fed biorelevant media, fm,fast and fm,fed are the fraction of drug in fasted and fed mixed micelles (or fat globules in FeSSGF), DD is the free drug diffusivity, DD−M, fast and DD−M, fed are the fasted and fed mixed micelle (or fat globule) diffusivity, and [Dt,fast] and [Dt,fed] are the total drug solubilities in fasted and fed-state biorelevant media, respectively. Solubility, particle size measurement, and intrinsic dissolution studies were performed for model BCS Class II drugs griseofulvin, ketoconazole, and ibuprofen each in FaSSGF, FeSSGF, FaSSIF-V2, and FeSSIF-V2 to compare observed versus predicted dissolution enhancement in fed-state over fasted-state biorelevant media. Relative to solubilization, in vitro dissolution was many fold lower in fed media over fasted media, indicating the compromising role of micellar and fat-globule diffusivity in attenuating dissolution rate based on solubility enhancement alone. Results of ϕfood agreed with what was observed and were also corroborated by reported food effects in vivo for griseofulvin, ketoconazole, and ibuprofen. The understanding of attenuation of in vitro dissolution in fed versus fasted biorelevant media may contribute towards predicting in vivo food effects, including lack of in vivo food effect for some poorly water soluble drugs.

A thermodynamic approach for predicting thermodynamic phase behaviors of pharmaceuticals in biorelevant media

Biorelevant solubilities of drugs are important fundamental data in pharmaceutical development. However, there is still no effective theoretical model to quantitatively describe and predict biorelevant solubility. Therefore, a theoretical modeling approach was proposed for predicting biorelevant solubility. Probenecid (PBD) and flurbiprofen (FBU) were chosen as model drugs. A pH-dependent solubility model was developed to accurately capture the influence of pH adjusted by various buffer systems on solubility, and the micellar effect was described by a micellar solubilization model. Based on the combination of the two models, biorelevant solubility was successfully modeled as a function of temperature, pH, surfactant type and concentration. Several predictive applications were proposed, including predicting the solubility of crystalline and amorphous drugs in biorelevant media with different formulations. These findings demonstrated that the developed theoretical approach achieved quantitative prediction of biorelevant solubility, which is expected to provide important theoretical prediction methodology and fundamental data for the development of drugs as well as their formulations.

Comparison of a single pharmaceutical surfactant versus intestinal biorelevant media for etravirine dissolution: Role and impact of micelle diffusivity

Etravirine is an antiviral whose oral absorption is limited by low solubility/dissolution. The objective was to predict and compare etravirine’s surfactant-mediated dissolution into polyoxyethylene-10 lauryl ether (POE) and FeSSIF-V2, including the contribution of slow micelle diffusivity. Dynamic light scattering (DLS) was used to measure the size and diffusivity values of drug-loaded micelles. In vitro intrinsic dissolution into surfactant media were predicted using a model for surfactant-mediated dissolution. Compared to maleic buffer, POE and FeSSIF-V2 increased etravirine solubility 232-fold and 8.97-fold, respectively. From DLS, micelle diffusivity of drug-loaded POE micelle and FeSSIF-V2 mixed-micelle was 5.15x10−7 cm2/s and 5.76x10−8 cm2/s, respectively. Observed and predicted dissolution enhancement into POE were 50.7 and 31.3, and 1.26 and 1.24 into FeSSIF-V2, respectively. Hence, there was high dissolution enhancement into POE, although the observed enhancement was only 21.9% of the observed solubility enhancement, reflecting the attenuating impact of the large and slowly diffusing drug-loaded POE micelles. Meanwhile, there was minimal dissolution enhancement into FeSSIF-V2, and the observed enhancement was only 14.0% of the observed solubility enhancement, reflecting the even slower diffusing drug-loaded FeSSIF-V2 mixed-micelles compared to drug-loaded POE micelles. Results are considered in light of designing a single pharmaceutical surfactant system for dissolution that mimics a FeSSIF-V2 system.