Low Solubility Drugs Research Articles

Development and formulation of itraconazole capsule by using reliable dispersion technique for solubility enhancement

Solid dispersions enhance the bioavailability and dissolution rate of the drugs by increasing the solubility of low soluble drugs. Different methods are employed in the preparation of Solid Dispersions such as kneading technique, co-precipitation technique, hot-melt extrusion technique, fusion technique, solvent technique, etc. Solid Dispersions has used various types of carriers to enhance the solubility of low soluble drugs. In this paper to overcome the drawback of adaptive solid diffusion methods and also to recover the bioavailability of itraconazole without crystalline change, we have used the following itraconazole, poloxamer, Sporanox, citric acid and PVP to prepare the solid diffusions. Itraconazole, poloxamer, Sporanox chemical are supplied by the various chemical supplier like Hemmi Pharma, BASF Chemical, Korea-Hanssen Pharm respectively. Solid diffusion the properties of carters on the solubility of itraconazole has experimented. Also, the dissolution and stability have been investigated and evaluated with commercial chemicals such as Sporanox which consist of 100 mg itraconazole. Hence it is crucial to show the changes in a crystalline form of the drug for a minimum of 6 months to shows the stability of the presented dispersion approach. Thus, developed formulation shows the importance of solubility without crystalline change by improving the bioavailability and increased the solubility of the drug.

Enhancing the solubility of nitazoxanide with solid dispersions technique: formulation, evaluation, and cytotoxicity study

Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an antiparasitic, antibacterial and antiviral agent. NTZ is a highly low aqueous soluble drug which possesses solubility of 0.00755 mg/mL and typically low bioavailability of 1%. Low aqueous solubility is usually regarded as prime prerequisites for enhanced absorption and bioavailability. The purpose of this study is to improve in vitro dissolution of the poorly soluble drug NTZ through amorphous solid dispersion technology. Three solid dispersions of NTZ were successfully prepared by hot-melt technique. It was further evaluated for drug content, DSC, XRD, SEM, TEM, FT-IR, in-vitro drug release study, in vitro MTT safety on HEK-293 and A-549 and stability study. The results of XRD showed after the formation of solid dispersions. The number of crystalline peaks has disappeared and confirmed the amorphous form of the drug. An in vitro release study showed that NTZ effectively released from solid dispersion into a simulated gastric releasing medium (pH 1.2). Further, the cytotoxicity study gave an indication of safe for human. Also, stability studies depicted no evident difference in the physical state of solid dispersion after six months. Hence, it can be concluded that the newly developed formulation was found to be safe and stable with enhanced solubility profile.

Rifabutin-Loaded Nanostructured Lipid Carriers as a Tool in Oral Anti-Mycobacterial Treatment of Crohn's Disease.

Oral anti-mycobacterial treatment of Crohn’s disease (CD) is limited by the low aqueous solubility of drugs, along with the altered gut conditions of patients, making uncommon their clinical use. Hence, the aim of the present work is focused on the in vitro evaluation of rifabutin (RFB)-loaded Nanostructured lipid carriers (NLC), in order to solve limitations associated to this therapeutic approach. RFB-loaded NLC were prepared by hot homogenization and characterized in terms of size, polydispersity, surface charge, morphology, thermal stability, and drug payload and release. Permeability across Caco-2 cell monolayers and cytotoxicity and uptake in human macrophages was also determined. NLC obtained were nano-sized, monodisperse, negatively charged, and spheroidal-shaped, showing a suitable drug payload and thermal stability. Furthermore, the permeability profile, macrophage uptake and selective intracellular release of RFB-loaded NLC, guarantee an effective drug dose administration to cells. Outcomes suggest that rifabutin-loaded NLC constitute a promising strategy to improve oral anti-mycobacterial therapy in Crohn’s disease.

A Review on Recent Technologies and Patents on Silica Nanoparticles for Cancer Treatment and Diagnosis.

Cancer is a condition in which some cells in the body grow uncontrollably and can also spread in other parts of the body. Among males, oral and lung cancers account for 25 % cancer deaths, while in females, breast and oral cancers cause 25% death. Breast and cervical cancers are the underlying cause of the high mortality rate among women. Owing to limitations of conventional cancer therapy like low drug specificity, less solubility, multidrug resistance, poor access to tumor cells and low bioavailability development of environmentally sensitive and target specific nanocarriers are imperative. The objective of this study is to review advancements made in techniques to synthesize Mesoporous Silica Nanoparticles (MSN's) as well as strategies to functionalize its silanol group for site-specific drug release in the tumor environment and to review recent patents published regarding it. To describe rationale for selection of MSN's for cancer theranostics amidst other nanocarriers developed. In the first section of this review, the physical and chemical properties of MSNs making it an ideal delivery system for cancer therapy and diagnostics are discussed. In the next section, various techniques involved in synthesizing and loading MSNs, including the influence of basic components of MSNs and reaction conditions on its properties are reviewed. Then the wide application of MSNs and various exogenous and endogenous stimuli harnessed for site-specific delivery of cargo and recent patents on modifying environmental conditions for large scale synthesis of MSNs and its active targeting for cancer treatment and bioimaging are discussed. Physico-chemical properties and synthetic protocols of MSNs justifying them to be a promising nanovector to overcome the ill effects of traditional chemotherapy. The superlative attributes of MSNs including, tunable size, morphology, high load volume, stability, ease of modifying external and internal surface leverage applications in various dimensions of therapeutics, diagnostics, and combinatorial drug delivery. MSNs surface functionalization can be harnessed for passive and active targeting by either coating the surface with polymers or attaching various ligands. An ideal nano-carrier must have high loading efficiency, easily detectable, and must have stimuli's sensitive, site-specific drug release. The patent study explores new dimensions on MSNs synthesis by claiming new cost-effective templates and silica source, a more safe environment for synthesis, reducing synthesis steps, duration of reaction, effective loading of low solubility drugs by magnetized nanocarriers, pathogen-specific release and development of novel photoluminescent rechargeable MSNs under mild conditions. It's a challenging task for researchers to successfully translate their prototypes to industries and make it feasible for commercialization. We can further work on excellent targeting concepts and architecture of MSNs for the increased opportunity in cancer theranostics.

Dissolution/permeation with PermeaLoop™: Experience and IVIVC exemplified by dipyridamole enabling formulations

It is our hypothesis that the presence of an absorptive sink for in-vitro dissolution experiments is decisive to predict extent and duration of super-saturation of low soluble drugs in formulations expected to increase oral absorption, often called enabling formulations. Combined dissolution-/permeation-testing may provide such absorptive sink. Commonly used in-vitro dissolution-/permeation tools have a limited interfacial area-to-donor-volume-ratio (A/V), far below the physiological one which is estimated for humans. In consequence, super-saturation is expected to be more pronounced and thus precipitation to occur more readily in these models as compared to the in-vivo situation. In the current study, a PermeaLoop™ prototype a of a novel in-vitro dissolution-/permeation-tool with a substantially larger A/V was employed to investigate the dissolution and permeation behaviour of model formulations of dipyridamole containing fumaric acid as modifier of the micro-environmental pH. After identifying the most suitable experimental conditions in terms of donor- and acceptor pH and composition, dose, flow-rate and sampling intervals, both the dissolution and the permeation were simultaneously assessed over time and the extent and duration of super-saturation monitored. The importance of biomimetic media in the donor was revealed not only in terms of increasing the dissolution but also the permeation. The formulations were ranked in terms of their performance (cumulative amount permeated). As a result the data generated by PermeaLoop experiments showed for the same formulations a superior correlation with in rat bioavailability data than obtained from a traditional side-by-side Dissolution-/Permeation-system with a Caco-2-cell membrane (D/P-system).The insights into the effects of solubilisers and pH conditions gained in the present study contribute to an improved mechanistic understanding of dynamic dissolution/permeation behaviour of weakly basic drugs and their enabling formulations. Challenges with the current PermeaLoop prototype are still to be solved, as dispersed drug still tends to get stuck inside the system, but gained experiences are helpful for the improvement of the design.

Spontaneous In Situ Formation of Liposomes from Inert Porous Microparticles for Oral Drug Delivery.

Despite the wide-spread use of liposomal drug delivery systems, application of these systems for oral purposes is limited due to their large-scale formulation and storage issues. Proliposomes are one of the formulation approaches for achieving solid powders that readily form liposomes upon hydration. In this work, we investigated a dry powder formulation of a model low-soluble drug with phospholipids loaded in porous functionalized calcium carbonate microparticles. We characterized the liposome formation under conditions that mimic the different gastrointestinal stages and studied the factors that influence the dissolution rate of the model drug. The liposomes that formed upon direct contact with the simulated gastric environment had a capacity to directly encapsulate 25% of the drug in situ. The emerged liposomes allowed complete dissolution of the drug within 15 min. We identified a negative correlation between the phospholipid content and the rate of water uptake. This correlation corroborated the results obtained for the rate of dissolution and liposome encapsulation efficiency. This approach allows for the development of solid proliposomal dosage formulations, which can be scaled up with regular processes.

Extraction of information about structural changes in a semisolid pharmaceutical formulation from near‐infrared and Raman images by multivariate curve resolution–alternating least squares and ComDim

AbstractSolid dispersions are an interesting option to improve the solubility of Class II (high permeability, low water solubility) drugs of the Biopharmaceutical Classification System without the use of organic solvents. However, structural changes (polymorphism) may be present in both active pharmaceutical ingredients (API) and excipients, which require evaluation during pharmaceutical development. Thus, the aim of this work was to demonstrate the feasibility of using Raman and near‐infrared (NIR) mapping associated with multivariate curve resolution–alternating least squares (MCR‐ALS) and common components and specific weights analysis (CCSWA or ComDim) chemometric methods to assess the solid dispersions of atorvastatin calcium in Gelucire® 48/16 under controlled (3.0 ± 1.0°C, sealed flask) and accelerated (33.0 ± 1.0°C, 75% of relative humidity, open flask) aging conditions. MCR‐ALS allowed the identification of the amorphous and crystalline fractions of the drug within the solid dispersion, which is not easily achieved by traditional techniques such as differential scanning calorimetry and X‐ray diffraction, especially for semisolid formulations. ComDim results indicated that Raman seemed more sensitive to the presence of the API, whereas NIR was found to be more sensitive to alterations in the spectra of the excipient. The use of the ComDim method is not yet widespread in the pharmaceutical area; therefore, this paper shows its potential to support pharmaceutical development in preformulation stages for stability studies.

Exploring the Impact of Morphology on the Properties of Biodegradable Nanoparticles and Their Diffusion in Complex Biological Medium.

Nanoparticle morphology (size, shape, and composition) and surface chemistry are the determining factors underpinning the efficacy of such materials in therapeutic applications. The size, shape, and surface chemistry of a nanoparticle can strongly influence key properties such as interactions with diverse biological fluids and interfaces and, in turn, impact the delivery of bioactive cargo, modulating therapeutic performance. This is exemplified in ocular drug delivery, where potential therapeutics must navigate complex biological media such as the gel-like vitreal fluid and the retina. Biodegradable block copolymer amphiphiles are a robust tool for the engineering of various types of self-assembled nanoparticles with diverse morphologies ranging from spherical and tubular polymersomes to spherical and worm-like micelles. Here, we explore the effect of morphological features such as shape and surface chemistry upon the interactions of a series of copolymer nanoparticles with retinal (ARPE-19) cells and the release of a low solubility drug (dexamethasone) that is currently used in ocular therapy and study their diffusion in vitreous using ex vivo eyes. We demonstrate that both aspect ratio and surface chemistry of nanoparticles will influence their performance in terms of cell uptake, drug release, and diffusion with high aspect ratio shapes demonstrating enhanced properties in relation to their spherical counterparts.

Improving Solubility of Poorly Soluble Abiraterone Acetate by Cocrystal Design Aided by In Silico Screening

Abiraterone acetate (ABI) is a BCS class IV (low solubility and low permeability) drug, and it was approved by the US FDA with brand name Zytiga in April 2011 for patients suffering from metastatic...

Evaluation of physicochemical properties and dissolution studies on quality control of low water solubility drugs (raw materials and pharmaceutical formulations)

The purpose of this study was to evaluate physicochemical properties and dissolution studies of furosemide (FUR), hydrochlorothiazide (HCTZ) and nifedipine (NIF), low water solubility drugs, in raw materials and pharmaceutical formulations. Surface and physicochemical characterization techniques -scanning electronic microscopy (SEM), thermogravimetry (TG), X-ray diffraction (XRD) and infrared (IR) spectrometry- as well as physical and physicochemical tests on tablets and capsules were applied as supporting information on drug quality control. Simple, rapid, and efficient UV-Vis methods were developed and validated for the determination of FUR, HCTZ and NIF samples. SEM exhibited considerable differences in the crystal morphological structures. Among the drugs studied, except for furosemide, more than one polymorph was present in the samples. Drug release profiles were satisfactory for all products. FUR and HCTZ tablets exhibited similar dissolution profiles, with very rapid release to the pharmaceutical specialties (reference, similar and generic). For HCTZ tablets, the similar drug (f2= 48.74) is not equivalent to the reference drug. NIF capsules (reference and compounded) showed a release ≥80% of stated on product labels, in 10 minutes. The results obtained in this study suggest that the quality parameters and drug dissolution profiles may have been influenced by the morphology and size of the crystals, excipients, and technological processes.

Anticrystal Engineering of Ketoprofen and Ester Local Anesthetics: Ionic Liquids or Deep Eutectic Mixtures?

Ionic liquids (ILs) and deep eutectic mixtures (DEMs) are potential solutions to the problems of low solubility, polymorphism, and low bioavailability of drugs. The aim of this work was to develop and investigate ketoprofen (KET)-based ILs/DEMs containing an ester local anesthetic (LA): benzocaine (BEN), procaine (PRO) and tetracaine (TET) as the second component. ILs/DEMs were prepared via a mechanosynthetic process that involved the mixing of KET with an LA in a range of molar ratios and applying a thermal treatment. After heating above the melting point and quench cooling, the formation of supercooled liquids with Tgs that were dependent on the composition was observed for all KET-LA mixtures with exception of that containing 95 mol% of BEN. The KET-LA mixtures containing either ≥ 60 mol% BEN or 95 mol% of TET showed crystallization to BEN and TET, respectively, during either cooling or second heating. KET decreased the crystallization tendency of BEN and TET and increased their glass-forming ability. The KET-PRO systems showed good glass-forming ability and did not crystallize either during the cooling or during the second heating cycle irrespective of the composition. Infrared spectroscopy and molecular modeling indicated that KET and LAs formed DEMs, but in the KET-PRO systems small quantities of carboxylate anions were present.

Characterization of Antineovascularization Activity and Ocular Pharmacokinetics of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GNE-947.

The objectives of the present study were to characterize GNE-947 for its phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitory activities, in vitro anti-cell migration activity in human umbilical vein endothelial cells (HUVECs), in vivo antineovascularization activity in laser-induced rat choroidal neovascular (CNV) eyes, pharmacokinetics in rabbit plasma and eyes, and ocular distribution using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) and autoradioluminography. Its PI3K and mTOR K i were 0.0005 and 0.045 µM, respectively, and its HUVEC IC50 was 0.093 µM. GNE-947 prevented neovascularization in the rat CNV model at 50 or 100 µg per eye with repeat dosing. After a single intravenous injection at 2.5 and 500 μg/kg in rabbits, its plasma terminal half-lives (t 1/2) were 9.11 and 9.59 hours, respectively. After a single intravitreal injection of a solution at 2.5 μg per eye in rabbits, its apparent t 1/2 values were 14.4, 16.3, and 23.2 hours in the plasma, vitreous humor, and aqueous humor, respectively. After a single intravitreal injection of a suspension at 33.5, 100, 200 μg per eye in rabbits, the t 1/2 were 29, 74, and 219 days in the plasma and 46, 143, and 191 days in the eyes, respectively. MALDI-IMS and autoradioluminography images show that GNE-947 did not homogenously distribute in the vitreous humor and aggregated at the injection sites after injection of the suspension, which was responsible for the long t 1/2 of the suspension because of the slow dissolution process. This hypothesis was supported by pharmacokinetic modeling analyses. In conclusion, the PI3K/mTOR inhibitor GNE-947 prevented neovascularization in a rat CNV model, with t 1/2 up to approximately 6 months after a single intravitreal injection of the suspension in rabbit eyes. SIGNIFICANCE STATEMENT: GNE-947 is a potent phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor and exhibits anti-choroidal neovascular activity in rat eyes. The duration of GNE-947 in the rabbit eyes after intravitreal injection in a solution is short, with a half-life (t 1/2) of less than a day. However, the duration after intravitreal dose of a suspension is long, with t 1/2 up to 6 months due to low solubility and slow dissolution. These results indicate that intravitreal injection of a suspension for low-solubility drugs can be used to achieve long-term drug exposure.

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems.

Today, dendrimers are the main nanoparticle applied to drug delivery systems. The physicochemical characteristics of dendrimers and their versatility structural modification make them attractive to applied as a platform to bioactive molecules transport. Nanoformulations based on dendrimers enhance low solubility drugs, arrival to the target tissue, drugs bioavailability, and controlled release. This review describes the latter approaches on the transport of bioactive molecules based on dendrimers. The review focus is on the last therapeutic strategies addressed by dendrimers conjugated with bioactive molecules. A brief review of the latest studies in therapies against cancer and cardiovascular diseases, as well as future projections in the area, are addressed.

Measurement solubility of Acetylsalicylic Acid in water and alcohols

Low aqueous solubility of drug is one of the problems in pharmaceutical industry and the enhancement of the solubility of these poorly soluble drugs has recently attracted the consideration of researchers. In this way, one of the essential methods to overcome this challenge is to use co-solvents. In this study, a set of experiments was conducted to measure the solubility and density of Acetylsalicylic Acid as a painkiller drug in water, 1-octanol, ethanol, methanol, and ethylene glycol as solvents in the temperature range of 298 to 330 K. Furthermore, the experiments are carried out at 298K in the binary mixture of solvents to investigate the interaction effect of another solvent or anti-solvent in different percentages of mixtures. The results of this investigation revealed that using binary solution of water and ethanol, as a solvent aid, was able to increase the solubility especially in high percentage of ethanol. Moreover, to indicate the applicability of simple empirical model, the experimental data was used to optimize two adjustable parameters of the selected model. In future research, a successful thermodynamic models will be offered based on gathered data for prediction of solubility in the different temperature with high accuracy.

The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs.

Among the significant problems of modern pharmacology are the low solubility and bioavailability of drugs. One way to resolve this problem is to obtain new polymorphic forms of drugs with improved physicochemical properties. Various approaches have been developed with this aim, including the preparation of co-crystals, the use of nanoparticles, or the use of compounds in the form of a salt. A promising direction in pharmacology concerns the production of new stable polymorphic structures. In this mini-review, we consider certain aspects of drug polymorphism, methods for the synthesis of polymorphs, and the stability, size, and transformation of crystalline polymorphs. Moreover, we summarize our results from several studies demonstrating the problems associated with the synthesis of new polymorphous modifications based on inert gases and cryotemperatures. The results indicate that the problems specific to drug polymorphisms have only been partly resolved, are of current interest, and require further development.

Formulation development and evaluation of immediate release tablet of terbinafine hydrochloride

The immediate release tablet of antifungal drug Terbinafine hydrochloride were prepared developed and evaluated to increase solubility and bioavailability of low soluble drug by using wet granulation method. The tablets were prepared by varying concentrations and compositions of microcrystalline cellulose, sodium starch glycolate, hydroxyl propyl methyl cellulose, magnesium stearate, and colloidal silicon dioxide for seven trial batches. The drug excipient compatability study was studied by photostability study. No significant changes were observed in photostability study. The tablets were evaluated for disintegration test, content uniformity, and friability. Invitro drug release profile Terbinafine hydrochloride was examined in four different media PH0.1N HCL, PH4.5 acidic buffers, PH6.8 phosphate buffer and PH3.0 citrate buffer for 45 minutes. The drug release for trial batch no.7 shows 100.4% of drug release and innovator shows 102% of drug release. The formulation trial no 6 and 7 showed no significant changes during the study period of accelerated stability study for 3 months. The result of all formulation 7 showed that good developed formulation of immediate release tablet containing Terbinafine hydrochloride drug was similar to the marketed product with all respect and stable to effect of temperature and humidity.

Ionic Liquid Forms of the Antimalarial Lumefantrine in Combination with LFCS Type IIIB Lipid-Based Formulations Preferentially Increase Lipid Solubility, In Vitro Solubilization Behavior and In Vivo Exposure.

Lipid based formulations (LBFs) are commonly employed to enhance the absorption of highly lipophilic, poorly water-soluble drugs. However, the utility of LBFs can be limited by low drug solubility in the formulation. Isolation of ionizable drugs as low melting, lipophilic salts or ionic liquids (ILs) provides one means to enhance drug solubility in LBFs. However, whether different ILs benefit from formulation in different LBFs is largely unknown. In the current studies, lumefantrine was isolated as a number of different lipophilic salt/ionic liquid forms and performance was assessed after formulation in a range of LBFs. The solubility of lumefantrine in LBF was enhanced 2- to 80-fold by isolation as the lumefantrine docusate IL when compared to lumefantrine free base. The increase in drug loading subsequently enhanced concentrations in the aqueous phase of model intestinal fluids during in vitro dispersion and digestion testing of the LBF. To assess in vivo performance, the systemic exposure of lumefantrine docusate after administration in Type II-MCF, IIIB-MCF, IIIB-LCF, and IV formulations was evaluated after oral administration to rats. In vivo exposure was compared to control lipid and aqueous suspension formulations of lumefantrine free base. Lumefantrine docusate in the Type IIIB-LCF showed significantly higher plasma exposure compared to all other formulations (up to 35-fold higher). The data suggest that isolation of a lipid-soluble IL, coupled with an appropriate formulation, is a viable means to increase drug dose in an oral formulation and to enhance exposure of lumefantrine in vivo.

An Overview on the Recent Technologies and Advances in Drug Delivery of Poorly Water-Soluble Drugs

Solubility can be defined as the amount of solute dissolved in a solvent at certain conditions to yield a single-phase system. Solubility of active pharmaceutical ingredients is considered the main parameter to get the most desired drug concentration in general circulation
 in order to achieve the desired therapeutic effect. Poor aqueous solubility considered the main problem occurs in the formulation progress of new chemical entities; in addition to the standard improvement; solubility is the main dispute for formulation scientists. The drug must appear as solution at the site of absorption in order to be absorbed. Many physical or chemical modification techniques are used to improve the solubility of low aqueous soluble drugs, in addition to other techniques such as particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant and complexation. The selection of the solubility improvement methods depends on drug characteristics, location of absorption and the features of the administered dosage form.

An Overview on the Recent Technologies and Advances in Drug Delivery of Poorly Water-Soluble Drugs

Solubility can be defined as the amount of solute dissolved in a solvent at certain conditions to yield a single-phase system. Solubility of active pharmaceutical ingredients is considered the main parameter to get the most desired drug concentration in general circulation in order to achieve the desired therapeutic effect. Poor aqueous solubility considered the main problem occurs in the formulation progress of new chemical entities; in addition to the standard improvement; solubility is the main dispute for formulation scientists. The drug must appear as solution at the site of absorption in order to be absorbed. Many physical or chemical modification techniques are used to improve the solubility of low aqueous soluble drugs, in addition to other techniques such as particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant and complexation. The selection of the solubility improvement methods depends on drug characteristics, location of absorption and the features of the administered dosage form.

Formulasi Self-Nanoemulsifiying Drug Delivery System (SNEDDS) Asam Mefenamat menggunakan VCO dengan Kombinasi Surfaktan Tween dan Span

Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) which has analgesic, anti-inflammatory and antipyretic effects. Mefenamic acid works by inhibiting prostaglandin synthesis as an inflammatory mediator. Mefenamic acid has low drug solubility and a long process of dissolution in the body which greatly affects the speed of absorption and bioavailability of the drug. In this study, mefenamic acid nanoemulsion formulation was carried out through a Self-Nanoemulsifying Drug Delivery System (SNEDDS) delivery system. SNEDDS is a drug delivery method through isotropic oil extraction, surfactants, cosurfactans and drug that form oil in water (m/a) emulsions which when in contact with the water phase in the digestive tract wiil from a nanoemulsion that occurs spontaneously so that the drug dissolves with a particle size small so as to increase the effective surface area for absorption. The purpose of the study was to determine the ratio of surfactant and cosurfactant composition to the optimum formula of SNEDDS of mefenamic acid with VCO as an oil phase. The SNEDDS formula was obtained by mixing the surfactants tween 80 and span 80, cosurfactant PEG 400 and VCO as the oil phase using the characterization of determining the optimum formula, namely emulsion formation, transmittance and emulsification time. The composition of the optimum formula of SNEDDS of mefenamic acid is 1 mL VCO; 1 mL PEG 400; 6 mL tween 80; 1 mL span 80. Optimum formula showed clear emulsion results, with transmittance values of 89,04% and emulsification time under 1 minute. In this study produced the optimum formula SNEDDS the met the criteria based on droplet size parameters of 153,5 nm, potential zeta value of 8,2 mV and showed good stability.