Solid Self-nanoemulsifying Drug Delivery System Research Articles

Enhanced Anti-Inflammatory Activity of Kaempferia galanga Extract by Solid Self-Nanoemulsifying Drug Delivery System and Its Development in Fast Disintegrating Tablet

The increasing global incidence of osteoarthritis (OA) emphasizes the need for effective treatments, particularly for the elderly. Conventional OA treatments pose administration challenges, leading to patient discomfort due to difficulties in administration. Herbal formulations offer an alternative to mitigate these issues. Kaempferia galanga (KG) contains ethyl p-methoxycinnamate, a compound displaying anti-inflammatory properties that hold promise for OA treatment. This study explores the formulation of a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Kaempferia galanga extract (KGE) and evaluates its anti inflammatory efficacy, subsequently developing it into a fast disintegrating tablet (FDT) dosage form. Initially, a liquid SNEDDS (L-SNEDDS) was prepared with varying surfactant and co surfactant concentrations. The optimal formula of L-SNEDDS (FL2) using tween 80: cremophor RH 40: PEG 400 in a ratio of 1:1:2 demonstrated favorable characteristics, including transmittance of 86.93 ± 1.16%, emulsification time of 28 ± 2.65 s, particle size of 27.79 ± 2.00 nm, PDI of 0.21 ± 0.014, and zeta potential of -12.57 mV. FL2 was solidified using aerosil 200 to produce S-SNEDDS and tested for anti-inflammatory efficacy in vivo using a carrageenan induced rat model. Results showed enhanced anti-inflammatory efficacy of KGE via S-SNEDDS, marked by reduced edema volume. Afterward, FDT S-SNEDDS were prepared using the direct compression method by comparing different types of superdisintegrants. The formulation using the combination of crospovidone and croscarmellose sodium (FT2) demonstrated excellent flow properties, tablet disintegration time of 63 s, wetting time of 34.01 ± 7.87 s, friability of 0.19%, and hardness of 3.53 ± 6.16 kg/cm2. The dissolution test indicated a better dissolution profile for FT2 compared to other formulations. In conclusion, this research presents the potential of FDT S-SNEDDS as a promising drug delivery system for enhancing the therapeutic effects of Kaempferia galanga extract in treating inflammatory conditions such as osteoarthritis.

Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications.

This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs.

Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, In-vitro, Ex-vivo and In-vivo assessment.

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53±5.371nm and 0.282±0.020, respectively. DST-S-SNEDDS revealed significantly lower IC50 (1.825μg/mL) than free DST (7.298μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

Advances in Nanoemulsion Formulations for Enhanced Drug Delivery: A Comprehensive Review

Abstract: Nanoemulsions (NEs) have emerged as adaptable medication delivery methods with extensive applications in both pharmaceuticals and cosmeceuticals. This comprehensive review delves into the myriad advantages of NEs, ranging from enhanced drug absorption to providing stability for chemically unstable compounds. NEs exhibit promising potential as substitutes for liposomes, offering improved performance in various formulations. In the realm of cosmeceuticals, NEs play a pivotal role in enabling rapid skin penetration while maintaining skin moisturization, thanks to their visually appealing coating. Their ability to deliver active ingredients efficiently makes them an attractive option for cosmetic formulations seeking enhanced efficacy. Moreover, this review sheds light on the involvement of NEs in antimicrobial therapies and gene therapy, underscoring their versatility and potential in addressing diverse medical challenges. Additionally, NEs find applications in commercial disinfectants, further highlighting their broad utility beyond traditional drug delivery systems. Furthermore, the review discusses innovative strategies, such as solid self-nanoemulsifying drug delivery systems (S-SNEDDS), which offer advantages in terms of stability, drug loading capacity, and patient compliance. By exploring these strategies, researchers aim to overcome existing limitations and optimize the therapeutic potential of NEs.

Establishment of nanoparticle screening technique: A pivotal role of sodium carboxymethylcellulose in enhancing oral bioavailability of poorly water-soluble aceclofenac

A novel nanoparticle screening technique was established to mostly enhance the aqueous solubility and oral bioavailability of aceclofenac using nanoparticle systems. Among the polymers investigated, sodium carboxymethylcellulose (Na-CMC) showed the greatest increase in drug solubility. Utilizing spray-drying technique, the solvent-evaporated solid dispersion (SESD), surface-attached solid dispersion (SASD), and solvent-wetted solid dispersion (SWSD) were prepared using aceclofenac and Na-CMC at a weight ratio of 1:1 in 50 % ethanol, distilled water, and ethanol, respectively. Using Na-CMC as a solid carrier, an aceclofenac-loaded liquid self-emulsifying drug delivery system was spray-dried and fluid-bed granulated together with microcrystalline cellulose, producing a solid self-nanoemulsifying drug delivery system (SNEDDS) and solid self-nanoemulsifying granule system (SNEGS), respectively. Their physicochemical properties and preclinical assessments in rats were performed. All nanoparticles exhibited very different properties, including morphology, crystallinity, and size. As a result, they significantly enhanced the solubility, dissolution, and oral bioavailability in the following order: SNEDDS ≥ SNEGS > SESD ≥ SASD ≥ SWSD. Based on our screening technique, the SNEDDS was selected as the optimal nanoparticle with the highest bioavailability of aceclofenac. Thus, our nanoparticle screening technique should be an excellent guideline for solubilization research to improve the solubility and bioavailability of many poorly water-soluble bioactive materials.

Solid self-nanoemulsifying drug delivery systems of nimodipine: development and evaluation

BackgroundThis study aimed to formulate solid self-nanoemulsifying drug delivery systems (SNEDDS) for nimodipine (NIM). The selection of Cremophor RH 40, Lipoxol 300, and PEG 400 as oil, surfactant, and co-surfactant was based on solubility and self-emulsification assessments. A ternary phase diagram determined the optimal oil to Smix (surfactant/co-surfactant) ratio (40:60). By utilizing liquid SNEDDS (NIM-SNEDDS) as an adsorbate and chitosan EDTA microparticles, developed through spray drying (SD-CHEM) and solvent evaporation (SE-CHEM) as adsorbents, the solid SNEDDS were created (NIM-SD-SSNEDDS and NIM-SE-SSNEDDS, respectively).ResultsBoth solid formulations exhibited favourable drug loading (NIM-SD-SSNEDDS = 79.67 ± 2.97%, NIM-SE-SSNEDDS = 77.76 ± 4.29%), excellent flowability, and drug amorphization as per XRD and DSC analysis. Scanning electron microscopy revealed smoothening and filling of adsorbent surfaces by adsorbate (with size range NIM-SD-SSNEDDS = 10–15 μm, NIM-SE-SSNEDDS = 20–25 μm). FTIR confirmed no interaction of drug and excipients. Stability studies demonstrated the physical and thermodynamic stability of reconstituted nanoemulsions with droplet size, PDI, zeta potential, emulsification time, % transmittance and cloud temperature for NIM-SD-SSNEDDS as 247.1 nm, PDI 0.620, 1.353 mV, 38–41 s, 94.64%, 54 °C and for NIM-SE-SSNEDDS as 399.6 nm, PDI 0.821, 1.351 mV, 40–48 s, 92.96%, 49 °C, respectively. FE-SEM images showed globules formed with small sizes, and there was no coalescence evidence, implying the reconstituted nanoemulsions' stability. In vitro dissolution studies revealed a fourfold increase in drug dissolution for NIM-SD-SSNEDDS (84.43%) and NIM-SE-SSNEDDS (76.68%) compared to pure drug (28%). Ex vivo permeation studies indicated almost similar profiles for NIM-SD-SSNEDDS (22.61%) and NIM-SE-SSNEDDS (21.93%) compared to NIM-SNEDDS (25.02%).ConclusionNIM-SD-SSNEDDS exhibited superior performance compared to NIM-SE-SSNEDDS, highlighting the efficacy of microparticles developed by the spray drying method (SD-CHEM) as adsorbents for solidification. These results suggest enhanced dissolution and permeation for nimodipine in both the solid SNEDDS.

Unveiling the Preparation and Characterization of Lercanidipine Hydrochloride in an Oral Solid Self-Nanoemulsion for Enhancing Oral Delivery.

Chronic kidney disease (CKD) is becoming increasingly prevalent worldwide, particularly among the elderly, along with an increase in the incidence of hypertension and cardiovascular disorders. Developing lipid-based oral dosage forms with a higher expected bioavailability of antihypertensive drugs with nephroprotective effects poses a challenge. Lercanidipine hydrochloride (LRCH) is a newer type of third-generation dihydropyridine calcium channel blocker that functions as an antihypertensive and has significant nephroprotective effects. Due to its extensive first-pass metabolism, its bioavailability is about 10% and increases to 3-4 times when taken with a high-fat meal. Targeting this drug to the lymphatic system using the solid self-nano-emulsifying drug delivery system (SSNEDDS) is a promising approach for improving LRCH's bioavailability and dispersion rate. SSNEDDS combines the benefits of both liquid self-emulsifying and solid dosage forms, improving drug stability and extending storage time. In this study, liquid SNEDDS composed of 10% peppermint oil, 67% Tween 20, and 22.5% propylene glycolwas solidified using two adsorbent agent mixtures (SSNEDDS1: Avicel PH 101 and Aerosil 200) and (SSNEDDS2: Avicel PH 102 and Aerosil 200) separately. The prepared formulations were evaluated for powder flow, drug content, and an in-vitro dispersion test in comparison to the brand-marketed tablet as a standard or pure drug. DSC and X-ray diffraction analysis were also used. The SSNEDDS2 shows excellent flowability, a higher drug content (99.761%), and a significantly higher and faster dispersion rate of 100% within 10 minutes compared to 92% of the marketed LRCH tablet and 18.1% of the pure drug for 60 minutes. The solid-state characterization of the formulation composed of SSNEDDS2 confirmed that the LRCH was in an amorphous form inside the solidified nano system without interacting with the excipient. This study successfully prepared LRCH using the promising strategy of SSNEDDS as a hard gelatin capsule with a higher dispersion rate. It improved its stability and expected bioavailability compared to the brand-marketed tablet as the standard.

Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery.

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.

Solid Self-Nanoemulsifying Drug Delivery Systems of Furosemide: In Vivo Proof of Concept for Enhanced Predictable Therapeutic Response.

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 μL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 μL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.

Quality by design aided self-nano emulsifying drug delivery systems development for the oral delivery of Benidipine: Improvement of biopharmaceutical performance

The primary objective of the research effort is to establish efficient solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for benidipine (BD) through the systematic application of a quality-by-design (QbD)-based paradigm. Utilizing Labrafil M 2125 CS, Kolliphor EL, and Transcutol P, the BD-S-SNEDDS were created. The central composite design was adopted to optimize numerous components. Zeta potential, drug concentration, resistance to dilution, pH, refractive index, viscosity, thermodynamic stability, and cloud point were further investigated in the most efficient formulation, BD14, which had a globule size of 156.20 ± 2.40 nm, PDI of 0.25, zeta potential of −17.36 ± 0.18 mV, self-emulsification time of 65.21 ± 1.95 s, % transmittance of 99.80 ± 0.70%, and drug release of 92.65 ± 1.70% at 15 min. S-SNEDDS were formulated using the adsorption process and investigated via Fourier transform infrared spectroscopy, Differential scanning calorimeter, Scanning electron microscopy, and powder X-ray diffraction. Optimized S-SNEDDS batch BD14 dramatically decreased blood pressure in rats in contrast to the pure drug and the commercial product, according to a pharmacodynamics investigation. Accelerated stability tests validated the product’s stability. Therefore, the development of oral S-SNEDDS of BD may be advantageous for raising BD's water solubility and expanding their releasing capabilities, thereby boosting oral absorption.

The role of synbiotics in Alzheimer`s management

AbstractBackgroundQuercetin and Lactobacillus Brevis were used in the development of S‐SNEDDS for their antiinflammaging effect in Alzheimer`s diseaseMethodThe isotropic mixture was prepared by incorporating Capmul MCM, Tween 80 and Transcutol P as oil, surfactant and co surfactant phases respectively. Quercetin was then added. The probiotic mixture was selected as a solid carrier and drug loading was calculated. The droplet size and zeta potential was also determined. The formulation was also assessed for differential scanning colorimetry (DSC), powder x ray diffraction studies (PXRD), and field emission scanning electron microscopy studies (FESEM). Stability studies of the developed formulation was also carried out. Alzheimer’s disease was induced in rats by the use of aluminum chloride (100mg/kg) after taking necessary permission from the institution animal ethical committee. The Morris water maze (MWM) test was used to assess the animals 48 hours following the last treatment. Utilizing marketed ELISA kits, the concentrations of TNF, IL‐1, and IL‐6 were determined.ResultQuercetin was solubilized in the isotropic mixture. The drug loading was found to be 93.4±0.75% for the liquid SNEDDS (QUE‐L‐SNEDDS) formulation. The droplet size of QUE‐L‐SNEDDS was found to be 73.24±1.45nm and had a zeta potential of ‐23.21±1.34 mV. Whereas, the solid SNEDDS (QUE‐LB‐S‐SNEDDS) was found to be 74.56±1.23 nm and had a zeta potential of ‐21.43 mV, respectively. This indicated that there was no change in the L‐SNEDDS and S‐SNEDDS formulation. Further, the amorphous nature of quercetin was confirmed by the DSC, PXRD and FESEM studies. Aluminum chloride was successful in inducing Alzheimer`s disease in the rats. Impaired learning and memory impairments, increased short‐term memory loss, and decreased locomotor activity were all observed in the negative controls. The developed formulation was successful in reversing the inflammatory effects of Alzheimer’s disease.ConclusionThe present study reveals that Quercetin and Lactobacillus Brevis can be used as a symbiotic combination as well as an adjuvant therapy in the treatment of inflammation related to Alzheimer’s disease. The results reveal an interesting outcome at the preclinical level and warrants future studies aimed at other plant based polyphenolic compounds especially in neurodegenerative diseases such as Alzheimer’s disease.

Impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system and self nano-emulsifying granule system

The purpose of this study was to investigate the impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system (SNEDDS) and self nano-emulsifying granule system (SEGS). The mesoporous calcium silicate (Ca-silicate) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were utilised as hydrophobic carrier and hydrophilic carrier, respectively. The liquid SNEDDS formulation, composed of Tween80/Kollipohr EL/corn oil (35/50/15%) with 31% (w/w) dexibuprofen, was spray-dried and fluid-bed granulated together with Avicel using Ca-silicate or HP- β-CD as a solid carrier, producing four different solid SNEDDS and SEGS formulations. Unlike the Ca-silicate-based systems, spherical shape and aggregated particles were shown in HP-β-CD-based solid SNEDDS and SEGS, respectively. Molecular interaction was detected between Ca-silicate and the drug; though, none was shown between HP-β-CD and the drug. Each system prepared with either carrier gave no significant differences in micromeritic properties, crystallinity, droplet morphology, size, dissolution and oral bioavailability in rats. However, the HP-β-CD-based system more significantly improved the drug solubility than did the Ca-silicate-based system. Therefore, both carriers hardly affected the properties of both solid SNEDDS and SEGS; though, there were differences in the aspect of appearance, molecular interaction and solubility.

Enhancement of Icariin Aphrodisiac Effect by Solid-SNEDDS Method Using Shark Liver Oil Phase

The Epimedium brevicornu Maxim plant contains icariin, a flavonoid compound known for its aphrodisiac effects. However, icariin has low solubility and bioavailability. This study aims to find the best formula for S-SNEDDS icariin, its physical properties, characteristics, and aphrodisiac activity. Using the S-SNEDDS (Solid-Self Nanoemulsifying Drug Delivery System) method with shark liver oil phase is expected to increase the solubility and bioavailability of icariin. The optimum formula used is tween 80 (72.5%): PEG 400 (13.75%) and shark liver oil (13.75%). The optimal formula of S-SNEDDS icariin with the adsorption method to solid carriers requires aerosol 200 as much as 783±28.86mg per 1mL. S-SNEDDS icariin has characteristics with an average emulsification time of 12.88±0.26 seconds, transmittance value of 98.08±0.94%, droplet size 171.8±8.9 nm, zeta potential -35.2±1.1 mV, flow speed less than 10 seconds, resting angle 35.159°. The dissolution test of S-SNEDDS icariin is better than icariin instead of S-SNEDDS. S-SNEDDS icariin dose 50 mg/KgBW has a better aphrodisiac effect than pure icariin 100 mg/kgBW.

Development and optimization of Ropinirole loaded self-nanoemulsifying tablets

BackgroundThe present research work aims to develop a Ropinirole-loaded self-Nanoemulsifying Drug Delivery system. Ropinirole has limited oral bioavailability due to substantial first-pass metabolism, which ultimately results in poor oral bioavailability and reduces plasma drug concentration and an overall reduction in therapeutic effects. Avoiding hepatic first-pass metabolism by increasing lymphatic uptake is the goal of the creation of the Ropinirole Self-NanoEmulsifying System. The solvent system for the liquid Self-NanoEmulsifying Drug Delivery System (SNEDDS) was optimized using Box-Behnken Design, where the concentration of oil(X1), surfactant (X2), and co-surfactant(X3) were taken as independent variables. The formulated liquid SNEDDS were then converted into solid SNEDDS by the adsorption method for improving patient compliance.ResultsThe obtained mean droplet size of the formulated SNEDDS was 96.71 nm, and the rate of emulsification was 22 s. Liquid SNEDDS was converted into solid SNEDDS using Syloid 244 FP as adsorbent. Scanning Electron Microscopy (SEM) study shows well-separated particles adsorbed on Syloid 244 FP. In vitro drug release studies show better release from solid and liquid SNEDDS when compared to pure suspension.ConclusionsRopinirole-loaded SNEDDS can be a better option for reducing the extensive first-pass metabolism associated with Ropinirole.

Self-nanoemulsifying drug delivery system (SNEDDS) of docetaxel and carvacrol synergizes the anticancer activity and enables safer toxicity profile: optimization, and in-vitro, ex-vivo and in-vivo pharmacokinetic evaluation.

Docetaxel (DTX) is a first-line chemotherapeutic molecule with a broad-spectrum anticancer activity. On the other hand, carvacrol (CV) has anti-inflammatory, antioxidant, cytotoxic, and hepatoprotective properties that could reduce undue toxicity caused by DTX chemotherapy. Thus, in order to overcome the challenges posed by DTX's poor aqueous solubility, low permeability, hepatic first pass, and systemic toxicities, we have developed a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) co-loaded with DTX and CV. In the present investigation, liquid-SNEDDS (L-SNEDDS) were fabricated using Nigella sativa oil, Cremophor RH 40, and Ethanol which was converted into solid by lyophilization using Aerosil 200. The reconstituted CV-DTX-S-SNEDDS showed an average globule size of < 200nm with promising flow properties (angle of repose θ: 33.22 ± 0.06). Additionally, 2.3-fold higher dissolution of DTX was observed from CV-DTX-S-SNEDDS after 6h as compared to free DTX. Similar trend was followed in dialysis release experiments with 1.5-fold higher release within 24h. Ex vivo permeation studies demonstrated significantly increased permeation of 1077.02 ± 12.72μg/cm2 of CV-DTX-S-SNEDDS after 12h. In vitro cell cytotoxicity studies revealed 5.2-fold reduction in IC50 as compared to free DTX in MDA-MB-231 cells. Formulation was able to induce higher apoptosis in cells treated with CV-DTX-S-SNEDDS as compared to free DTX and CV. It was evident from toxicity studies that CV-DTX-S-SNEDDS was well tolerated at higher dose where CV was able to manage the toxic effects of free DTX. In vivo pharmacokinetic study showed 3.4-fold increased Cmax and improved oral bioavailability as compared to free DTX. Thus, CV-DTX-S-SNEDDS could be an encouraging option for facilitating DTX oral therapy.

Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.