Liquid Self-nanoemulsifying Drug Delivery System Research Articles

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.

Novel lipid-based nanocarrier of nitrofurantoin for improved oral bioavailability and reduced variability in absorption

The current research aims to improve oral bioavailability, reduce the variability in absorption, and decrease GI intolerance of Nitrofurantoin (NFT) by presenting in a lipid-based liquid self-nanoemulsifying drug delivery system (L-SNEDDS). L-SNEDDS formulations were developed using a thermosolvency technique. Physicochemical properties including in-vitro drug diffusion were exercised to optimize the formula, further, comparative ex-vivo permeability, in-vitro cell line, in-vitro anti-microbial, and in-vivo pharmacokinetic evaluation of optimized formulation was carried out. Based on the highest saturation solubility, soybean oil, oleoyl polyoxyl-6-glycerides, and diethylene glycol monoethyl ether were selected as oil, surfactant, and co-surfactant, respectively. A Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size (59.4 ± 0.8 nm), optimum zeta potential (−21.3 ± 1.1 mV), and faster drug release (95.4 ± 4.2 % in 30 min), and hence was selected for further evaluation. Optimized formulation (SF5) was found stable and showed improved membrane permeability against pure drug suspension (1.84 times) and marketed suspension formulation (1.15 times). SF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. However, it showed the highest zone of inhibition against both the gram-negative and gram-positive organisms. The relative bioavailability of NFT-loaded L-SNEDDS was enhanced by 1.46 and 1.55 times compared to the marketed and pure drug, respectively. Thus, it can be concluded that the variability of oral absorption is minimized, and oral bioavailability is improved by the novel lipid-based nanocarrier system of NFT.

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.

Development and evaluation of Simvastatin based SNEDDS for treatment of Alzheimer’s disease

AbstractBackgroundThe purpose of this research work to improve solubility and bioavailability of Simvastatin using self nano‐emulsifying drug delivery system (SNEDDS) for treatment the Alzheimer’s disease.MethodSelf emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co‐surfactants. Validation of method for accuracy, repeatability, Interday and intraday precision, ruggedness, and robustness were within the acceptable limits. The liquid SNEDDS was prepared and optimized using ternary phase diagram, thermodynamic, centrifugation and cloud point studies.ResultThe globule size of optimized formulations was less than 200 nm which could be acceptable nanoemulsion size range. The mean droplet size, drug loading, PDI and zeta potential were found to be 141.0 nm, 92.22%, 0.23 and ‐10.13 mV and 153.5nm, 93.89%,0.41 and ‐11.7 mV and 164.26 nm, 95.26%, 0.41 and ‐10.66mV respectively. The best formulations were subjected to FESEM for surface morphology.ConclusionFormulation development, and evaluation of simvastatin loaded self nano‐emulsifying drug delivery system (SNEDDS) for treatment the Alzheimer’s disease were carried out.

Optimization and characterization of self-nanoemulsifying drug delivery system of iloperidone using box-behnken design and desirability function

Iloperidone (IP) is an antipsychotic drug which belongs to Biopharmaceutical Classification System (BCS) II exhibiting poor aqueous solubility. The current investigation explores the possibility of enhancement of solubility and dissolution characteristics of IP by formulation of liquid self-nano emulsifying drug delivery system (L-SNEDDS) utilizing Box-Behnken Design (BBD) and desirability function. The oils, surfactants and co-surfactants used in the study were selected based on solubility of the drug and their emulsification ability. Optimization of the formulation was performed using BBD by employing four response variables such as globule size (nm), percentage transmittance (%), self-emulsification time (sec) and percent drug released in 15min. 2D contour plots and 3D response surface plots were constructed using Design Expert software. The developed optimal L-SNEDDS of IP through BBD approach resulted in improvement of solubility and dissolution rate as compared with the pure drug. Based on desirability function, optimized formulation was prepared and was assessed for response variables (globule size, percentage transmittance, self-emulsification time and percent drug dissolved in 15min). The characterization studies revealed droplet size to be 21.80±2.41nm, 99.584±0.65% transmittance, 24.43±2.12sec emulsification time and 95.31±1.57% cumulative drug release in 15min. The results conclude the potentiality of prepared L-SNEDDS in improving solubility and dissolution rate of IP.

Solubility Enhancement of Poorly Soluble Drug Ezetimibe by Developing Self Nano Emulsifying Drug Delivery System

Objectives: To enhance solubility, dissolution, and permeability of poorly water-soluble drug Ezetimibe (EZE) using a self-nano emulsifying drug delivery system (SNEDDS). Methods: Initially, the solubility of the EZE was determined in various oils and buffers. Surfactants and co-surfactants were screened based on the solubility of the drug in oil as per the emulsification efficacy test. Liquid SNEDDS was developed and characterized. Solid SNEDDS was developed and characterized using optimized liquid SNEDDS followed by the development of EZE-loaded Tablet SNEDDS. Finding: Liquid SNEDDS (LSNEDDS) was formulated using Capmul MCM C8 EP, Cremophore RH 40, and Labrafil M 2125 CS as oil, surfactant, and co-surfactant respectively. Optimized L-SNEDDS formulation was found to be efficient with an average %T of 99.5%, drug content of 98.43%, flask inversion 0 numbers, and the average particle size of 36.7 nm, zeta potential of -57.5 mV, Polydispersibility index in of 0.119. Also, the in vitro release profile of drug from L-SNEDDS encapsulated in hard gelatin capsules was evaluated in different dissolution media viz. simulated gastric fluid and simulated intestinal fluid. For the drug, more than 95% cumulative release was observed within 30 min exclusive of the pH of the medium. The L-SNEDDS were adsorbed on a solid support and then mixed with tablet blends and compressed into tablets. Further, no adverse changes in globule size, shape, the zeta potential of SNEDDS, and dissolution profile were apparent on conversion to solid powder form and tablet form. Novelty: The developed liquid SNEDDS form of EZE showed enhanced solubility, dissolution, and permeability in comparison to pure drugs. Conversion of L-SNEDDS to PSNEDDS would be a novel approach to overcome the limitations associatedwith liquid dosage forms. Keywords: Ezetimibe (EZE); Selfnano emulsifying drug delivery system (SNEDDS); liquid SNEDDS (L SNEDDS); powder SNEDDS (PSNEDDS); Tablet SNEDDS (TSNEDDS)

Optimization of a Cefuroxime Axetil-Loaded Liquid Self-Nanoemulsifying Drug Delivery System: Enhanced Solubility, Dissolution and Caco-2 Cell Uptake.

Cefuroxime axetil (CA) is an oral cephalosporin which hydrolyzes rapidly to the active parent compound cefuroxime. CA is known to have incomplete oral bioavailability (30–50%) due to its poor solubility and enzymatic conversion to cefuroxime in the gut lumen. In order to overcome these drawbacks, a lipid-based self-nanoemulsifying drug delivery system (SNEDDS) has been developed and optimized. The SNEDDS formulations were prepared using the aqueous phase titration method. The greatest self-emulsifying area was found in the 2:1 Smix ratio. As a result, different SNEDDS formulations were carefully selected from this phase diagram based on their smaller droplet size < 100 nm, polydispersity index ≤ 0.5, dispersibility (Grade A), and transmittance (%) > 85%. Thermodynamic stability tests were carried out in order to rule out any metastable/unstable SNEDDS formulations. The droplet size, polydispersity index, zeta potential, and entrapment efficiency (% EE) of optimized CA-loaded SNEDDS (C-3) were 18.50 ± 1.83 nm, 0.064 ± 0.008, −22.12 ± 1.20 mV, and 97.62 ± 1.06%, respectively. In vitro release studies revealed that the SNEDDS formulation had increased CA solubility. CA-SNEDDS-C3 increased CA cellular uptake, possibly due to increased CA solubility and the inhibition of enzymatic conversion to cefuroxime. Finally, in terms of the improvement of oral bioavailability, CA-loaded-SNEDDS could be a viable alternative to commercially available CA formulations.

Formulation and Evaluation of Solid Self Nano Emulsifying drug delivery System of Olanzapine to Enhance Aqueous Solubility and Dissolution Rate

Present research work was aimed to enhance aqueous solubility and dissolution rate of olanzapine by solid self nano emulsifying drug delivery system(S-SNEDDS). Olanzapine is a BCS class II drug having 65% oral bioavailability; it is used in the treatment of psychosis, depression and mania conditions. Oils, Surfactants, Co surfactants were selected depending upon the saturated solubility of olanzapine in those components; excipients were screened depending on olanzapine solubility in various oils, surfactants and co surfactants. Surfactant: co surfactant {Smix} ratios i.e., 3:1 and 4:1 were prepared to determine nano emulsion regions and also to formulate liquid self nano emulsifying drug delivery system (L-SNEDDS). Pseudo ternary phase diagram were plotted by using Triplot version 4.1.2 software, nano emulsion region was determined and evaluated. Formulations were designed based on saturated solubility of olanzapine and Pseudo ternary phase diagram using various ratios of oils [Capryol 90], surfactants [Kolliphor EL], co surfactants [Lauroglycol 90] depending on its solubility and nano emulsion formation four formulations were developed which are further selected for characterisation of L-SNEDDS like robustness to dilution, self emulsification, determination of droplet size, PDI, Drug loading efficacy, zeta potential and also Invitro drug release. Among those four formulations, F1 (SB184J 4:6) was optimum because compared to other three formulations F3 gave best results in terms of droplet size (66nm) with PDI (0.24), Invitro drug release, dissolution rate of F1 SNEDDS having (88.201± 0.25%). Invitro drug release of F1 formulation was compared with that of Olanzapine [API] (45.281± 0.52%) the results indicating that there is a increase in solubility and dissolution rate of olanzapine by 2.2 times more compared to pure olanzapine (API). F1 (SB184J 4:6) were converted into S-SNEDDS by adsorption process by addition porous carriers (Aerosil 200). Formulated S-SNEDDS were undergone various evaluation parameters and also reconstitution parameters to determine Droplet size and Invitro drug release of solid F1 (SB184J4:6) formulation. The results of present study demonstrates that olanzapine SNEDDS has an ability and potential to enhance solubility and dissolution rate.

Self-nanoemulsifying composition containing curcumin, quercetin, Ganoderma lucidum extract powder and probiotics for effective treatment of type 2 diabetes mellitus in streptozotocin induced rats

Liquid self-nanoemulsifying drug delivery system (L-SNEDDS) of curcumin and quercetin were prepared by dissolving them in isotropic mixture of Labrafil M1944CS®, Capmul MCM®, Tween-80® and Transcutol P®. The prepared L-SNEDDS were solidified using Ganoderma lucidum extract, probiotics and Aerosil-200® using spray drying. These were further converted into pellets using extrusion-spheronization. The mean droplet size and zeta potential of L-SNEDDS were found to be 63.46 ± 2.12 nm and − 14.8 ± 3.11 mV while for solid SNEDDS pellets, these were 72.46 ± 2.16 nm and −38.7 ± 1.34 mV, respectively. The dissolution rate for curcumin and quercetin each was enhanced by 4.5 folds while permeability was enhanced by 5.28 folds (curcumin) and 3.35 folds (quercetin) when loaded into SNEDDS pellets. The Cmax for curcumin and quercetin containing SNEDDS pellets was found 532.34 ± 5.64 ng/mL and 4280 ± 65.67 ng/mL, respectively. This was 17.55 and 3.48 folds higher as compared to their naïve forms. About 50.23– and 5.57-folds increase in bioavailability was observed for curcumin and quercetin respectively, upon loading into SNEDDS pellets. SNEDDS pellets were found stable at accelerated storage conditions. The developed formulation was able to normalize the levels of blood glucose, lipids, antioxidant biomarkers, and tissue architecture of pancreas and liver in streptozotocin induced diabetic rats as compared to their naïve forms.

Development of mushroom polysaccharide and probiotics based solid self-nanoemulsifying drug delivery system loaded with curcumin and quercetin to improve their dissolution rate and permeability: State of the art

The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nanocarriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.

Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin.

Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X1 (oil) and X2 (surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15 min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 ± 1.170 nm, 0.228 ± 0.012, 17.660 ± 1.520 s, and 34.180 ± 1.380 mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were - 28.200 ± 1.200 mV, 99.200% ± 0.600, and 90 °C, respectively. Drug release was found to be 93.320% ± 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.

Formulation and Characterization of Piroxicam as Self-Nano Emulsifying Drug Delivery System

Piroxicam (PIR) is a nonsteroidal anti-inflammatory drug of oxicam category, used in gout, arthritis, as well as other inflammatory conditions (topically and orally). PIR is practically insoluble in water, therefore the aim is prepare and evaluate piroxicam as liquid self-nanoemulsifying drug delivery system to enhance its dispersibility and stability. The Dispersibilty and Stability study have been conducted in Oil, Surfactant and Co-surfactant for choosing the best materials to dissolve piroxicam. The pseudo ternary phase diagrams have been set at 1:1, 2:1, 3:1 as well as 4:1 ratio of surfactants and co-surfactants, also there are 4 formulations were prepared by using various concentrations of transcutol HP, cremophore EL and triacetin oil. All the constructed prepared formulas have been assessed for in vitro drug dissolution, thermodynamic stability, polydispersity index, robustness to dilution, particle size distribution, drug content, and the dispersibility and emulsification time.From the presented research concluded that the self-nanoemulsifying drug delivery system is the convenient method for improving Dispersibilty and Stability of piroxicam.&#x0D;  Keywords: Pseudo-ternary phase diagram, Dissolution rate, SNEDDS, Piroxicam.

Preparation and in-vitro evaluation of cilostazol self-emulsifying drug delivery system

This work reported a first liquid self-nanoemulsifying drug delivery system (SEDD) of cilostazol using oleic acid as oil phase, tween 80 as surfactant, and transcutol as co-surfactant. Cilostazol is a poor water-soluble phosphodiesterase III inhibitor, which has antiplatelet&#x0D;  &#x0D; and vasodilator effect used to relief intermittent claudication symptoms. Cilostazol solubility was determined in various oils, surfactants and co-surfactants and phase diagram was constructed at different oil: surfactant: co-surfactant ratios to determine the existence of nano-emulsion region. The in-vitro dissolution profile showed an optimized cilostazol SEDD formula (LT1) containing oleic acid (10%) as oil, tween 80 (45%) as surfactant, and transcutol (45%) as co-surfactant in comparison with the commercial conventionally Tablets. The LT1 formula was thermodynamically sTable, with a zeta potential of -30.48 mV and droplet size 154 nm. The LT1 capsule showed a superior dissolution profile (100%) when compared to the commercial Tablet (64%) of cilostazol.&#x0D; The objective of the present study is to formulate cilostazol as an oral liquid SEDD with better solubility and drug release to overcome a variable bioavailability of the commercial Tablet in which a high-fat meal increases absorption to approximately 90%. 

Preparation and in-vitro evaluation of cilostazol self-emulsifying drug delivery system

This work reported a first liquid self-nanoemulsifying drug delivery system (SEDD) of cilostazol using oleic acid as oil phase, tween 80 as surfactant, and transcutol as co-surfactant. Cilostazol is a poor water-soluble phosphodiesterase III inhibitor, which has antiplatelet and vasodilator effect used to relief intermittent claudication symptoms. Cilostazol solubility was determined in various oils, surfactants and co-surfactants and phase diagram was constructed at different oil: surfactant: co-surfactant ratios to determine the existence of nano-emulsion region. The in-vitro dissolution profile showed an optimized cilostazol SEDD formula (LT1) containing oleic acid (10%) as oil, tween 80 (45%) as surfactant, and transcutol (45%) as co-surfactant in comparison with the commercial conventionally Tablets. The LT1 formula was thermodynamically sTable, with a zeta potential of -30.48 mV and droplet size 154 nm. The LT1 capsule showed a superior dissolution profile (100%) when compared to the commercial Tablet (64%) of cilostazol. The objective of the present study is to formulate cilostazol as an oral liquid SEDD with better solubility and drug release to overcome a variable bioavailability of the commercial Tablet in which a high-fat meal increases absorption to approximately 90%.

Development and Validation of UV Spectroscopic Method for Estimation of Fisetin in Self Nanoemulsifying Drug Delivery System

Fisetin is a polyphenolic flavonoid which has been reported various pharmacological activities as a crude extract and in formulation form. This study was designed to develop and validate a simple and cost effective method for the estimation of fisetin in the liquid self nanoemulsifying drug delivery system (L-SNEDDS). Solutions having different concentration of fisetin were prepared in methanol to develop the calibration curve. The solutions were scanned at 362nm by using UV-spectrophotometer. Similarly, for validation of method recovery of drug was measured at three levels 80%, 100% and 120% of the mid concentration and data was recorded. Further, this method was used to measure the drug loading in L-SNEDDS of fisetin. The data was found to be linear in the range of 4–12μg/mL with regression coefficient of 0.999. The recovery of drug in the range of 95% to 105% indicated the accuracy of the method. The percentage relative standard deviation among all the responses was found to be less than 2% indicating the precision of the method. The LOD and LOQ was found to be 0.28 and 0.86μg/mL respectively. Drug loading in the L-SNEDDS was found to be 93.66%. A simple, accurate and cost-effective method for the estimation of the fisetin in pharmaceutical dosage forms was developed and validated using ultra violet spectroscopy.

Design and in vivo Evaluation of Manidipine by Self-Nanoemulsifying Drug Delivery Systems

The current research is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of Manidipine for enhanced solubility and oral bioavailability. The Manidipine SNEDDS are formulated with excipients comprising of Capmul MCM (oil phase), Transcutol P (surfactant) Lutrol L 300 as co-surfactant. The prepared fifteen formulations of Manidipine SNEDDS analysed for emulsification time, percentage transmittance, particle size, in vitro drug release, and stability studies. In vivo pharmacokinetic studies of the optimized formulation were carried out in Wistar rats in comparison with control (pure drug). The morphology of Manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 is 98.24 ± 5.14%. The particle size F14 formulation was 22.4 nm and Z-Average 23.3 nm. The PDI and zeta potential of Manidipine SNEDDS optimized formulation (F14) were 0.313 and-5.1mV respectively. From in vivo bioavailability data the optimized formulation exhibited a significantly greater Cmax and Tmax of the SNEDDS was found to be 3.42 ± 0.46ng/ml and 2.00 ± 0.05 h respectively. AUC0-∞ infinity for formulation was significantly higher (11.25 ± 3.45 ng.h/ml) than pure drug (7.45 ± 2.24ng. h/ml). Hence a potential SNEDDS formulation of Manidipine developed with enhanced solubility and bioavailability.

DESIGN AND EVALUATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS OF MANIDIPINE FOR ENHANCEMENT OF SOLUBILITY

Objective: The present work is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of manidipine.&#x0D; Methods: The manidipine SNEDDS is formulated with excipients comprising Capmul MCM as oil phase, Transcutol P as surfactant, and Lutrol L 300 as cosurfactant. The prepared fifteen formulations of manidipine SNEDDS were performed for emulsification time, percentage transmittance, particle size, drug release, in vitro dissolution and stability studies. Ternary phase diagram plotted using Chemix software.&#x0D; Results: The optimized manidipine liquid SNEDDS formulation (F14) subjected to drug-excipient compatibility studies by Fourier-transform infrared spectroscopy and characterized for particle size, zeta potential, scanning electron microscopy, and stability studies. The morphology of manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 (98.24±5.14%) was higher than that of pure drug (39.17±2.98%). The stability data indicated no noticeable change in drug content, emulsifying properties, drug release, and appearance.&#x0D; Conclusion: Hence, a potential SNEDDS formulation of manidipine developed with enhanced solubility, dissolution rate, and bioavailability.

Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals – Curcumin and thymoquinone

BackgroundCurcumin and Thymoquinone are very well-known phytochemicals for their potent anti-inflammatory and anticancer properties. The major challenges for curcumin is its poor aqueous solubility and erratic oral bioavailability. ObjectiveTo develop a novel liquid self-nanoemulsifying drug delivery system (SNEDDS) containing curcumin and thymoquinone and further converted into a solid dosage form using adsorbents Syloid® and Neusilin® as the solid carrier. MethodsThe characterization of the liquid and solid SNEDDS was performed by particle size & zeta potential analysis, scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and X-ray powder diffraction. The drug loading, and in vitro release studies were carried out to investigate the efficiency of curcumin release from SNEDDS. ResultsThe liquid SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. The results of characterization studies showed that solidification using 50% (w/w) Syloid® and Neusilin® in the liquid formulation yield free flowing powder with no agglomeration but Neusilin® produced smooth granules than Syloid® and kept the drugs stable in amorphous state. In vitro dissolution studies indicated that liquid SNEDDS formulations of F4 and its solid SNEDDS using Neusilin® provided high dissolution efficiency and reproducibility for curcumin and thymoquinone. However, Neusilin® showed higher rate of dissolution (more than 65%, p < 0.05) compared to Syloid® for curcumin. ConclusionsCurcumin loaded-SNEDDS formulation containing thymoquinone in liquid & solid dosage forms were successfully developed with an increased drug loading and dissolution rate, which could be the potential combined delivery system for various anti-inflammatory and anti-cancer treatments.

Self-nanoemulsifying Drug Delivery System of Mebendazole for Treatment of Lymphatic Filariasis

Lipid-based self-nanoemulsifying drug delivery system was explored to improve the oral bioavailability and target specificity of mebendazole for treatment of lymphatic worm infestations. Ternary phase diagrams were constructed to select suitable oil-surfactant mixture. Liquid self-nanoemulsifying drug delivery system consisting of Capmul MCM L8, Chromophore RH40 and tocopherol polyethylene glycol succinates a pre-concentrate was systematically optimized using 32 full factorial designs. β-cyclodextrin-based nanosponges were used to prepare solid self-nanoemulsifying drug delivery system. Characterization of liquid self-nanoemulsifying drug delivery system was carried out using percent transmission, globule size, zeta potential, polydispersity index and drug content. Globule size in the range of 50-90 nm and zeta potential of –5 to –12 mV was obtained, which co-related well with percent transmission. Powder X-ray diffraction, differential scanning calorimetry and scanning electron microscope of solid self-nanoemulsifying drug delivery system indicated the presence of mebendazole as a molecular dispersion. Ex vivo studies showed nearly five-fold increase in the flux. In vivo studies showed two-fold increase in bioavailability. Significant enhancement in drug dissolution and saturation solubility from solid self-nanoemulsifying drug delivery system resulted in an increase in the bioavailability. Besides this, greater surface area, improved release, P-gp modulation potential of excipients and lymphatic bypass via Peyer’s patches protected drug from hepatic first pass metabolism all of which would contribute to the observed improved bioavailability. Lymphatic transport of drug could achieve target specificity in lymphatic filariasis.

Analysis of 3D Prints by X-ray Computed Microtomography and\xa0Terahertz Pulsed Imaging

PurposeA 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI).MethodsPrinting was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined.ResultsA clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5 ± 0.75% larger than designed; n = 3).ConclusionsThe 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms.