Compounding Education in US PharmD Curricula.

OBJECTIVE: To determine the extent of compounding education (CE) offered in United States (US) doctor of pharmacy curricula. METHODS: A 24-item survey instrument addressing various aspects of CE was developed and validated. An email containing the link to the survey instrument was shared with instructors of compounding at 122 of 141 accredited schools and colleges of pharmacy in the US. RESULTS: Of these, 112 schools and colleges responded, rendering a survey response rate of 91.8%. Survey results indicate that CE is offered to a similar extent either as a required standalone course or as integrated instruction as part of a standard course. Whereas 70.8% of programs reported mostly hands-on training in CE in their curricula, there were about 11% programs that mostly offered didactic instruction in CE. Dispersed systems and semisolid formulations are the most prepared in nonsterile compounding, while proper hand washing, garbing, and gloving are the most taught techniques in sterile compounding. Compounding education is delivered principally by pharmaceutics faculty (62.3%) compared to practice faculty (32.1%). CONCLUSION: The survey determined the extent to which CE is addressed across different schools and colleges of pharmacy in the US. Although some institutions lack minimal nonsterile or sterile compounding facilities, they may improve by modeling the established programs in the country. Leadership at pharmacy institutions may need to allocate funds for CE, and support faculty who instruct in compounding.

AI & experimental-based discovery and preclinical IND-enabling studies of selective BMX inhibitors for development of cancer therapeutics.

The current work aims to design and provide a preliminary IND-enabling study of selective BMX inhibitors for cancer therapeutics development. BMX is an emerging target, more notably in oncological and immunological diseases. In this work, we have employed a predictive AI-based platform to design the selective inhibitors considering the novelty, IP prior protection, and drug-likeness properties. Furthermore, selected top candidates from the initial iteration of the design were synthesized and chemically characterized utilizing 1H NMR and LC-MS. Employing a panel of biochemical (enzymatic) and cancer cell lines, the selected molecules were tested against these assays. In addition, we used artificial intelligence to predict and evaluate several critical IND-focused physicochemical and pharmacokinetics values of the selected molecules. A secondary objective of the current work was also to validate the sole role of BMX in animal models known to be mediated by BMX. More than 50 molecules were designed in the present study employing five novel discovered scaffolds. Two molecules were nominated for further IND-focused studies. Compound II showed promising in-vitro activity against BMX in both enzymatic assays compared to other kinases and in cancer cell lines with known BMX overexpression. Interestingly, compound II showed very favorable physicochemical and pharmacokinetics properties as predicted by the used platforms. The animal study further confirmed the sole role of BMX in the disease model. The current work provides promising data on a selective BMX inhibitor as a potential lead for therapeutics development, and the asset is currently in the optimization stage. Notably, the current study shows a framework for a combined approach employing both AI and experimentation that can be used by academic labs in their research programs to more streamline programs into IND-focused to be bridged easily for further clinical development with industrial partners.

Sustained release of curcumin self-emulsifying drug delivery system (SEDDS) from solvent-cast Soluplus® films.

The objective of the present study was to investigate the feasibility of formulating and loading Curcumin SEDDS (Self-Emulsified Drug Delivery Systems) into films made from Soluplus® as the film-forming polymer. Films with up to 30% of Curcumin SEDDS were prepared by the solvent casting technique and analyzed for their mechanical and dissolution properties. A nine-run, two-factor, three-level factorial design was utilized to investigate the effect of SEDDS load (10, 20, and 30% w/w) and film thickness (10, 25, and 40 mils) on the tensile strength, elongation, and adhesiveness of the films. The dissolution profile of the films was also investigated by a USP Type 1 method. SEDDS loading was found to plasticize Soluplus® and to yield transparent films of good mechanical properties. Increasing SEDDS load, however, was found to reduce the tensile strength of the films, while increasing their adhesiveness and elongation. On the other hand, while an increase in film thickness was found to increase the tensile strength of the films, it reduced the elongation capacity of the films. Loading SEDDS into Soluplus® films was also found to sustain their release over 6 h, where a significant delay in release was found at lower SEDDS loads. This study demonstrated that Soluplus® can be used not only to formulate SEDDS into polymeric films but also to sustain their release over an extended time.

Preparation and characterization of aqueous vitamin E/Soluplus® dispersions for film coating applications.

OBJECTIVE: The goals of this study were to (1) delineate a technique to prepare stable aqueous vitamin E/Soluplus® dispersions; (2) characterize films cast from the aqueous dispersions; and (3) demonstrate the utility of the aqueous dispersions in fluid bed coating applications. This study demonstrated the feasibility of using vitamin E in the preparation of amphiphilic film withs potential use in delayed-release coating applications. METHODS: Low viscosity aqueous vitamin E/Soluplus® dispersions were prepared by first spray drying ethanolic vitamin E/Soluplus® solutions followed by high-shear homogenization of the solid dispersions in water. Concentrated (10%) aqueous dispersions containing 0%, 10%, 20%, and 30% of vitamin E in the binary blend with Soluplus® were then cast into films and characterized for contact angle and mechanical strength by texture analysis. RESULTS: All films were hydrophilic and homogenous, which confirmed the utility of vitamin E as a plasticizer for the Soluplus® polymer. The 0% and 10% films were brittle whereas the 30% were tacky. The 20% dispersion was subsequently used to coat acetaminophen granules by a fluidized bed process to a dry weight gain of 10-30%. When tested by a dissolution study, a delay in acetaminophen release was observed as a function of weight gain. CONCLUSION: The results from this study demonstrated that it is feasible to produce stable vitamin E/Soluplus® aqueous dispersions to be used as solvent-free functional film coating materials.

Modulation of the sublingual microenvironment and pH-dependent transport pathways to enhance atropine sulfate permeability for the treatment of organophosphates poisoning.

Atropine sulfate (AS) auto-injectors are the only approved antidote for out-of-hospital emergency treatment of organophosphates (OP) toxicity. However, they are only available for military use and require the administration of multiple auto-injectors. Therefore, an alternative, patient-friendly and more affordable fast-disintegrating sublingual tablets (FDSTs) of AS were previously developed. In this article, the effect of modifying the microenvironment's pH and/or using penetration enhancers on AS sublingual transport pathways were evaluated in an attempt to further enhance AS sublingual permeability. Ten different AS FDST formulations with or without the incorporation of alkalizer and various penetration enhancers were manufactured and characterized. AS permeability was investigated through excised porcine sublingual membrane using Franz cells. Results showed that the incorporation of either a transcellular enhancer or alkalizer achieved a significantly higher AS permeability enhancement (twofold). Combining sodium bicarbonate (Na Bicarb) 2% as alkalizer with sodium dodecyl sulfate (SDS) 1% as a transcellular enhancer resulted in the greatest synergistic enhancement in AS sublingual permeability (up to twelvefold). In conclusion, the modified AS FDST developed in this work has the potential to improve the pharmacokinetic parameters of AS following sublingual administration for the first-aid treatment of OP toxicity in future animal bioequivalency studies.

Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems.

Sulforaphane is an isothiocyanate compound that has been derived from cruciferous vegetables. It was shown in numerous studies to be active against multiple cancer types including pancreatic, prostate, breast, lung, cervical, and colorectal cancers. Sulforaphane exerts its therapeutics action by a variety of mechanisms, such as by detoxifying carcinogens and oxidants through blockage of phase I metabolic enzymes, and by arresting cell cycle in the G2/M and G1 phase to inhibit cell proliferation. The most striking observation was the ability of sulforaphane to potentiate the activity of several classes of anticancer agents including paclitaxel, docetaxel, and gemcitabine through additive and synergistic effects. Although a good number of reviews have reported on the mechanisms by which sulforaphane exerts its anticancer activity, a comprehensive review on the synergistic effect of sulforaphane and its delivery strategies is lacking. Therefore, the aim of the current review was to provide a summary of the studies that have been reported on the activity enhancement effect of sulforaphane in combination with other anticancer therapies. Also provided is a summary of the strategies that have been developed for the delivery of sulforaphane.

A full factorial experimental design to study the effect of flavoring agents on the mechanical properties of curcumin chewing gum tablets with high solids content.

Objective: Developing chewing gum tablets (CGTs) with high drug loads is a challenge due to the loss of mastication properties. We postulated that poor mastication properties of such gums could be improved by adjusting the concentration of liquid flavors to serve as plasticizers and consequently increase the flexibility of the elastomer in the gum base. To test this hypothesis, the objective of this work was to evaluate the effects of flavor type and concentration, and storage conditions on the textural properties of CGTs loaded with 20% curcumin (CUR) by weight.Methods: CGTs were made by directly compressing Health in Gum® base with CUR. The resultant CGTs were characterized by single and two bites textural tests to measure their yield strength, post-bite failure rate, and compressibility.Results: Flavor concentration (X2) had a significant impact on the masticatory properties of the chewing gums, which could be ascribed to the plasticizing effect of peppermint oil. Addition of liquid flavors and storage at low temperature (X4) produced CGTs with the desirable properties of low yield strength (Y1) and post-bite structural failure rate (Y2), and high compressibility (Y3). The effect of flavors however was negated at high temperatures, especially when flavored gums were stored for extended time at 50 °C. Flavor type (X1) on the other hand had no effect on the masticatory properties of the chewing gums.Conclusions: This study concluded that it is feasible to formulate CGTs with high solids content without negatively impacting their mechanical properties by controlling the concentration of liquid flavors.

Development and validation of a HPLC-UV method for the simultaneous detection and quantification of paclitaxel and sulforaphane in lipid based self-microemulsifying formulation.

Paclitaxel (PTX) and sulforaphane (SFN) are known anticancer molecules. Their activity was found to be potentiated when tested concurrently. Only recently, however, a novel SFN enabled PTX self-microemulsifying formulation (SMEDDS) was developed for their simultaneous delivery. This necessitated the development of an analytical method for the simultaneous detection and quantitation of PTX and SFN. In this study, a simple and sensitive isocratic high performance liquid chromatography-ultraviolet (HPLC-UV) analytical method was developed and validated per International Conference on Harmonization guidelines to satisfy this objective. Its application was demonstrated when quantifying the amount of PTX and SFN released from the SMEDDS in various dissolution media. The separation of the analytes was performed with the aid of a reversed phase C18 column at ambient temperature using a 60:40 mixture of acetonitrile and KH2PO4 buffer (pH 5.0) as the mobile phase. PTX and SFN peaks were detected at 202 nm with high resolution without interference from excipients. This method showed linearity within 2.5-100 µg/mL range with r2 > 0.999. The limit of detection and lower limit of quantitation were 0.1638 and 0.4964 µg/mL for PTX and 0.4419 and 1.3389 µg/mL for SFN, respectively. A total of 98-101% of the injected samples was recovered with RSD of 0.06-0.68% indicating the suitability of the method for the simultaneous detection and quantitation of the molecules in dissolution media.

Development and evaluation of paclitaxel nanoemulsion for cancer therapy.

Tocosol™ is a tocopherol-based paclitaxel (PTX) nanoemulsion consisting of α-tocopherol (α-T) isomer of vitamin E as a solubilizer and vitamin E TPGS as the primary emulsifier. Despite its positive attributes in early clinical studies, it failed the pivotal phase III clinical trials. The long-term goal of this work was to reformulate Tocosol™. In this study, Tocosol™ formulation was optimized by replacing the α-T isomer with the more pharmacological active isomer γ-tocotrienol (γ-T3), and the surfactant vitamin E TPGS was replaced with in-house designed PEGylated γ-T3 surfactant. The reformulated paclitaxel γ-T3/PEGylated γ-T3 -based nanoemulsion was significantly more active against pancreatic tumor cell lines than α-T/Vitamin E TPGS based formulation (IC50 = 0.5 µM and 1.1 µM, respectively). Furthermore, the reformulated product showed an average size of 220 ± 6 nm with surface charge equal to -42 ± 2 mV. The optimized product was physically and chemically stable over 6 months per ICH storage condition guidelines.

Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations.

Ceramide (Cer) is an active cellular sphingolipid that can induce apoptosis or proliferation-arrest of cancer cells. Nanoparticle-based delivery offers an effective approach for overcoming bioavailability and biopharmaceutics issues attributable to the pronounced hydrophobicity of Cer. Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug resistance. Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. Here, we report that new ceramide-rubusoside (Cer-RUB) nanomicelles considerably enhance Cer in vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation. Natural RUB encapsulated short-chain C6-Cer so as to form Cer-RUB nanomicelles (∼32 nm in diameter) that substantially enhanced Cer solubility and its levels in tissues and tumors of mice dosed intraperitoneally. Intriguingly, Cer-RUB nanomicelle treatments restored p53-dependent tumor suppression and sensitivity to cisplatin in OVCAR-3 ovarian cancer cells and xenograft tumors carrying p53 R248Q mutation. Moreover, Cer-RUB nanomicelles showed no signs of significant nonspecific toxicity to noncancerous cells or normal tissues, including bone marrow. Furthermore, Cer-RUB nanomicelles restored p53 phosphorylated protein and downstream function to wild-type levels in p53 R172H/+ transgenic mice. Altogether, this study, for the first time, indicates that natural Cer-RUB nanomicelles offer a feasible approach for efficaciously and safely targeting cancers carrying p53 missense mutations.

Gold nanoparticles and angiogenesis: molecular mechanisms and biomedical applications.

Angiogenesis is the formation of new blood vessels from pre-existing vessels. It is a highly regulated process as determined by the interplay between pro-angiogenic and anti-angiogenic factors. Under certain conditions the balance between angiogenesis stimulators and inhibitors is altered, which results in a shift from physiological to pathological angiogenesis. Therefore, the goal of therapeutic targeting of angiogenic process is to normalize vasculature in target tissues by enhancing angiogenesis in disease conditions of reduced vascularity and blood flow, such as tissue ischemia, or alternatively to inhibit excessive and abnormal angiogenesis in disorders like cancer. Gold nanoparticles (AuNPs) are special particles that are generated by nanotechnology and composed of an inorganic core containing gold which is encircled by an organic monolayer. The ability of AuNPs to alter vasculature has captured recent attention in medical literature as potential therapeutic agents for the management of pathologic angiogenesis. This review provides an overview of the effects of AuNPs on angiogenesis and the molecular mechanisms and biomedical applications associated with their effects. In addition, the main synthesis methods, physical properties, uptake mechanisms, and toxicity of AuNPs are briefly summarized.

Novel olive oil phenolic (-)-oleocanthal (+)-xylitol-based solid dispersion formulations with potent oral anti-breast cancer activities.

Epidemiological studies have compellingly documented the ability of the Mediterranean diet rich in extra-virgin olive oil to reduce the incidence of certain malignancies, and cardiovascular diseases, and slow the Alzheimer's disease progression. S-(-)-Oleocanthal (OC) was identified as the most bioactive olive oil phenolic with documented anti-inflammatory, anticancer, and anti-Alzheimer's activities. OC consumption causes irritating sensation at the oropharynx via activation of TRPA1. Accordingly, a taste-masked formulation of OC is needed for its future use as a nutraceutical while maintaining its bioactivity and unique chemistry. Therefore, the goal of this study was to prepare a taste-masked OC solid formulation with improved dissolution and pharmacodynamic profiles, by using (+)-xylitol as an inert carrier. Xylitol was hypothesized to serve as an ideal vehicle for the preparation of OC solid dispersions due to its low melting point and sweetness. The optimized OC-(+)-xylitol solid dispersion was physically and chemically characterized and showed effective taste masking and enhanced dissolution properties. Furthermore, OC-(+)-xylitol solid dispersion maintained potent in vivo anti-breast cancer activity. It effectively suppressed the human triple negative breast cancer development, growth, and recurrence after primary tumor surgical excision in nude mice orthotopic xenograft models. Collectively, these results suggest the OC-(+)-xylitol solid dispersion formulation as a potential nutraceutical for effective control and prevention of human triple negative breast cancer.

Novel liquid-liquid extraction and self-emulsion methods for simplified isolation of extra-virgin olive oil phenolics with emphasis on (-)-oleocanthal and its oral anti-breast cancer activity.

Epidemiological and clinical studies compellingly documented the ability of Mediterranean diet rich in extra-virgin olive oil (EVOO) to reduce breast and colon cancers incidence, cardiovascular diseases, and aging cognitive functions decline. (-)-Oleocanthal (OC) and other EVOO phenolics gain progressive research attention due to their documented biological effects against cancer, inflammations, and Alzheimer's disease. There is no simple, reliable, and cost-effective isolation protocol for EVOO phenolics, which hinder their therapeutic applications. This study develops novel methods to isolate OC and other EVOO phenolics. This includes the use of ultra-freezing to eliminate most EVOO fats and the successful water capacity to efficiently extract OC and EVOO phenolics as self-emulsified nano-emulsion. Subsequent resin entrapment and size exclusion chromatography afforded individual EVOO phenolics in high purity. OC in vitro and in vivo oral anti-breast cancer (BC) activities validated its lead candidacy. Effective isolation of EVOO phenolics provided in this study will facilitate future preclinical and clinical investigations and stimulate the therapeutic development of these important bioactive natural products.

STEMI mimicker in a 26-year-old man.

We herein describe a case of acute myocarditis which may mimic myocardial infarction, since affected patients experience 'typical' chest pain, the ECG changes are identical to those observed in acute coronary syndromes, and serum markers are increased. This case emphasises the importance of performing appropriate cardiac MRI to help in the differential and definitive diagnosis as well as the extent of myocardial involvement. ST elevation myocardial infarction is rare in young adults and when it is encountered, it should raise the differential diagnosis of its mimickers.

The physiochemical, mechanical, and adhesive properties of solvent-cast vitamin E/Soluplus® films.

Soluplus® is an amphiphilic graft copolymer used in hot melt extrusion applications and electrospinning. Very little information is available on the use of Soluplus® as a film former and in the development of film-based formulations. The overall aim of this work was to study the mechanical and adhesive properties of Soluplus® films prepared by the solvent casting technique. More specifically, we discovered that vitamin E can serve as a plasticizer for the Soluplus® polymer and to significantly modulate its mechanical and adhesive properties. Vitamin E (0-75% w/w) and Soluplus® were dissolved in ethanol and cast on liners to produce transparent films. Cast films were tested for their physiochemical properties by IR, XRD, and MDSC, and for their adhesive and mechanical properties by texture analysis. Vitamin E was found to be miscible with Soluplus® and to reduce the crystallinity of the films. Vitamin E also decreased the films' tensile strength and Young's modulus while significantly increasing their percent elongation. The most notable effect was the observed increase in the adhesiveness (tackiness) and hydrophobicity of the films, which was evidenced by a significant increase in their water contact angle and a decrease in their swelling capacity and disintegration. These observations indicated that vitamin E/Soluplus® blends might be used for the preparation of highly pliable films, especially when made with 30-50% vitamin E, and in the development of a new type of pressure sensitive adhesive films when prepared with ≥65% vitamin E load.

D-optimal mixture design: Formulation development, mechanical characterization, and optimization of curcumin chewing gums using oppanol® B 12 elastomer as a gum-base.

Curcumin (CUR) chewing gums have potential therapeutic benefits to head and neck cancer patients. The objective of this work was to develop medicated chewing gums (MCGs) with high CUR loading and desirable mastication properties. This was accomplished by evaluating the effect of five gum ingredients: (X1) polyisobutene, (X2) polyvinyl acetate, (X3) wood rosin, (X4) wax, and (X5) CUR on the mechanical properties of the MCGs using a 25-run, five-factor, two-level D-Optimal mixture design. CUR MCGs were prepared by the conventional fusion method for making chewing gums. They were characterized by a two-bites texture and uniaxial tension tests to generate force-displacement curves from which the cohesiveness (Y1), springiness (Y2), chewiness (Y3), compressibility (Y4), resistance to extension (Y5), and extensibility (Y6) were measured. Observed responses were used to generate polynomial models correlating the independent with the dependent variables. Elasticity and stiffness of the gums were found to be readily impacted by PIB and CUR levels. Fitted models were then used to predict a gum composition that has comparable mechanical properties to commercially procured chewing gums. The optimized MCG was loaded with 50% of either CUR or CUR/SBE-ß-CD inclusion complex and tested in vitro for drug release. Although no differences in mechanical properties were observed, substituting CUR with the inclusion complex was found to significantly enhance drug release. This study highlighted the impact of each gum ingredient on the quality of the MCGs and demonstrated the feasibility of preparing chewing gums with up to 50% drug loading.

Mechanical Characterization and Dissolution of Chewing Gum Tablets (CGTs) Containing Co-compressed Health in Gum® and Curcumin/Cyclodextrin Inclusion Complex.

Curcumin chewing gums could be therapeutically beneficial if used by the head and neck cancer patients. High curcumin loading in chewing gums however is needed to achieve desired therapeutic effect. Preparing gums with high drug load is nonetheless challenging because of the negative impact of solids on their masticatory properties. The use of liquid flavors was found to partially solve this problem. The objectives of this study were to (1) determine the maximum amount of curcumin that can be loaded into co-compressed chewing gums made from Health in Gum® as the base and flavored with 1.5% peppermint oil, (2) determine if addition of sweeteners can improve the yield strength and compressibility of the gums when examined by a texture analyzer, (3) examine the effect of temperature over a storage period of one month on the physical stability of the chewing gums, and (4) study the impact of substituting curcumin with its inclusion complex with SBE-ß-CD on drug release. It was found that when flavored, Health in Gum® could load up to 25% curcumin by weight without compromising its masticatory properties. When tested for drug release, SBE-ß-CD was found to significantly increase the amount of curcumin dissolved within 30 min. Despite poor drug release from gums loaded with insoluble curcumin, the fragmentation of the gums during mastication by the Erweka tester is nonetheless expected to produce a suspension for absorption in the lower GIT. This study demonstrated how modulating gum composition and storage conditions can impact the mechanical properties of chewing gums with high solids content.

Medicated Chewing Gums (MCGs): Composition, Production, and Mechanical Testing.

Medicated chewing gums (MCGs) represent a unique platform for drug delivery. They have been defined as solid single-dose preparations, which may contain more than one active pharmaceutical ingredient (API) with base consisting primarily of gum that has to be chewed for a certain period of time. They mainly contain a tasteless masticatory gum base as the core with other minor nonmasticatory ingredients, such as flavors and sweeteners. Despite their advantages in drug delivery, MCGs remain a niche product due to the complexity of their formulation, lack of acceptable testing methods, and intricacy of their manufacturing. Few studies have been reported on their use, and most of the information on their composition and production could be found in patent search. The aim of this review is to provide an overview of gum composition, manufacturing process, and characterization. Due to the scarcity of studies concerning the evaluation of the mechanical properties of MCGs, greater emphasis was placed on the available performance tests and procedures for the estimation of their mechanical and textural properties. While very few tests have been recommended by the official pharmacopeias, several tests have been suggested for assessing the mechanical properties of MCGs in vitro. Properties, such as chewiness, elasticity, and firmness, of chewing gums during mastication are imperative quality attributes that have been found to strongly correlate with gum composition and mouth feel.

The rheological and textural characterization of Soluplus®/Vitamin E composites.

Soluplus® is a graft amphiphilic copolymer that is frequently used as an excipient in solid dosage forms as a dissolution and a solubility enhancer. We discovered that Soluplus® can be dissolved in vitamin E. The result is a tacky and highly adhesive material. Our research objective was to evaluate the rheological, adhesive, and textural properties of the Soluplus®/Vitamin E composites. In this study, Soluplus® was dissolved under heat in vitamin E at increasing concentrations from 0 to 40% (by weight). The flow behavior of the Soluplus®/Vitamin E composites was determined by applying shear stress using an advanced AR2000 rheometer. Under the linear viscoelastic region (LVR), the rheological properties of the blends such as dynamic viscosity (η'), storage modulus (G'), loss modulus (G″), and the phase angle tangent (tan δ) were measured. Hardness, adhesiveness, and cohesiveness of the blends were also measured with a TA.XT plus texture analyzer. Rheological analysis showed that the viscosity of the Soluplus®/Vitamin E composites increased with an increase in Soluplus® concentration but decreased as the temperature increased from 20 to 90 °C. The adhesiveness of the blends also significantly increased with an increase in Soluplus® concentration. The results from this study indicated that Soluplus®/Vitamin E composites have the potential to be exploited in applications where the use of highly adhesive material is desirable.

Development of a new class of sulforaphane-enabled self-emulsifying drug delivery systems (SFN-SEDDS) by high throughput screening: A case study with curcumin.

Self-emulsifying drug delivery systems (SEDDS) have been used as a formulation strategy to overcome the challenges in formulating poorly water soluble drugs. The objective of the present study was to report on the solubilizing capacity of sulforaphane (SFN) and its utilization to formulate SEDDS of poorly water soluble drugs. A set of 24 drugs was tested for their solubility in SFN of which Cyclosporine A, Celecoxib, Paclitaxel, Docetaxel, and Curcumin were selected for subsequent SEDDS formulation development utilizing SFN as common solubilizer. SFN-SEDDS formulations were developed utilizing a step-wise screening method that enabled the selection of the most efficient surfactants and co-surfactants to yield transparent microemulsions by microscopic analysis and absorbance data. The optimized SEDDS formulation for curcumin was selected for further investigation by DSC and FTIR, and was subjected to a dissolution study where more than 95% of the drug was found to dissolve within 10 min in both simulated gastric and intestinal fluids. The physical stability of the SEDDS was also confirmed in both media when monitored at three different temperatures (4, 25 and 37 °C) up to 30 days. This study introduced a new approach to formulating SEDDS by utilizing the solubilizing capacity of SFN and introduced high throughput screening approach to formulation development and stability study.