Labrafil M1944CS Research Articles

Evaluation of a mucoadhesive auto-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration

This study investigated the potential of self-nanoemulsifying drug delivery systems (SNEDDS) to optimize the oral bioavailability of insulin. Insulin complexes with phospholipids and enzymatically-modified phospholipids were developed and incorporated into the SNEDDS using Lauroglycol FCC as the oily phase and Cremophor EL and Labrafil M1944CS as the surfactant and co-surfactant, respectively. Additionally, mucoadhesive polysaccharides (sodium alginate and guar gum) were added further to enhance the bioavailability of insulin in these systems. The objective was to increase the bioavailability and bioactivity of an insulin-modified phosphatidylcholine complex by incorporating mucoadhesives into the SNEDDS. After polymer inclusion, the resulting nanoemulsions exhibited droplet diameters ranging from 57 to 83 nm. Cytotoxicity and apparent permeability tests were conducted on Caco-2 and NIH 3 T3 cell lines, revealing that toxicity was related to the concentrations of insulin and surfactant in the nanosystems—formulations containing guar gum as a mucoadhesive showed better tolerance to cell death in the Caco-2 line. In a murine diabetes model, the SNEDDS were observed to reduce glucose levels by up to 61.63 %, with a relative bioavailability of 2.25 % compared to subcutaneously administered insulin. These results suggest that SNEDDS incorporating mucoadhesives could represent a promising strategy for improving oral insulin delivery.

Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98–16.56 folds on MCF-7 and CaCo2 cells and 47.82–98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5–1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.Graphical

Nanoemulsion-Based Strategy for Maximizing Nitrofurantoin Absorption: In-vitro and In-vivo Investigations.

The main objective of the current research work is to improve the absorption of Nitrofurantoin (NFT) by minimizing gastrointestinal (GI) intolerance and variations in its absorption by formulating the drug into a nanoemulsion (NE). Based on the highest saturation solubility of NFT, soybean oil, transcutol HP, and labrafil M1944CS were selected as oil, co-surfactant, and surfactant, and 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, highest zeta potential, and higher drug release and hence was selected for further evaluation. Optimized formulation (NF5) showed improved membrane permeability against pure drug suspension (2.30 times) and marketed suspension formulation (1.43 times). NF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. The relative bioavailability of NFT-NE was enhanced by 1.10 and 1.17 times compared to the marketed and pure drug suspension, respectively. Thus, it can be concluded that the optimized nanoemulsion formulation of NFT exhibited improved membrane permeability, comparable cell viability, and increased relative bioavailability. These findings suggest the potential of the nanoemulsion approach as a strategy to overcome the variability of oral absorption and GI intolerance of NFT.

Transdermal delivery of acemetacin loaded microemulsions: preparation, characterization, in vitro – ex vivo evaluation and in vivo analgesic and anti-inflammatory efficacy

The goal of this study was to see if microemulsions might be used as a transdermal drug delivery system for acemetacin (ACM). Microemulsions containing isopropyl myristate, Tween 80, Transcutol HP, Labrafil M1944 CS, ethanol, and distilled water were used to create pseudo-ternary phase diagrams. In microemulsion systems, the ultimate concentration of ACM was 1% (w/w). Conductivity, droplet size, zeta potential, polydispersity index, viscosity, and pH were used to characterize the microemulsions. Furthermore, in vitro permeability investigations were carried out utilizing diffusion cells derived from the dorsal skin of mice. The results of characterization studies such as droplet size, polydispersity index, zeta potential, conductivity values of ideal formulation were found 9.107 ± 1.588 nm, 0.283 ± 0.062, −0.313 ± 0.006 mV, 0.018 ± 0.012 µS/cm, respectively. The penetration of ACM from ideal formulation was greater than the other developed formulations. The anti-inflammatory effect of ACM was evaluated in mice using the paw edema test. In addition, all test microemulsions had a significant analgesic effect in the hot plate and tail-flick tests as compared to the control. Finally, microemulsion formulations might be used to deliver ACM transdermally.

Unveiling the dielectric properties of self-nanoemulsifying drug delivery systems (SNEDDS)

Self-nanoemulsifying Drug Delivery System (SNEDDS) improves the bioavailability of bioactive compounds that exhibit low water solubility. In this regard, our study aims to assess the formulation of SNEDDS in a wide range of oil concentrations (0–8.6 wt%) by dynamic light scattering, FTIR, dielectric measurements, and the characterization of the interface layer and its molecular interactions with water. The proper formulation of SNEDDS accounted for the lipophilic/hydrophilic balance leading to a homogeneous distribution of oil droplets in water with constant sizes of 20–22 nm, which does not depend on oil concentration. Dielectric spectroscopy measurements in the GHz frequency range allowed us to obtain the dependence of relaxation time as a function of oil concentration and its relationship with the viscosity of the nanoemulsion. The classical two-phase model of Hanai, Maxwell-Garnet, Bruggeman, and Lichtenecker fails to describe the dielectric properties of nanoemulsions. Therefore, in this work, a three-phase model is proposed to model the dielectric measurements, which include water as the continuous phase, oil droplets, and interface layer due to using Cremophor EL (HLB = 12–14) and Labrafil M1944CS (HLB = 2–3) as surfactant and co-surfactant. This model fits well with the experimental results and allows us to obtain SNEDDS properties such as the dielectric constant (20.9), volume fraction, and the interface layer thickness (ca. 5 nm). Investigated oil–water nanoemulsions can be a model for developing different drug delivery systems. Additionally, proposed measurements in the GHz frequency range and their interpretation can be generalized for nanoemulsion characterization.

엔잘루타마이드의 용해도 개선을 위한 고형의 자가나노유화 약물전달시스템

The objective of this study was to develop a novel enzalutamide-loaded solidified self-nanoemulsifying drug delivery system formulation with enhanced solubility and dissolution rate. Various oil and surfactant were screened, then Medium Chain Triglyceride oil and Polysorbate 80 and Labrafil M2125CS were selected as oil and a surfactant. Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, SNEDDS consisted of MCT oil (oil), Polysorbate 80 (surfactant) and Labrafil M2125CS (co-surfactant) at a weight ratio of 20:70:10. The SNEDDS produced the emulsion droplet size 18.66±0.88 nm. Spray drying technique was used to convert the selected enzalutamide-loaded SNEDDS into solid SNEDDS with inert carrier such as silicon dioxide. Enzlautamide-loaded solid SNEDDS was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffractometry, dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 15.37±0.49 nm and there was no change in particle size between with or without drug. SEM and PXRD results suggested that enzalutamide existed in amorphous form in enzalutamide-loaded solid SNEDDS. In addition, enzalutamide-loaded solid SNEDDS increased saturation solubility 42-fold and dissolution rates 23- fold compared to crystalline enzalutamide. Therefore, the solid SNEDDS could be a potential nano-sized drug delivery system for poorly water-soluble drug enzalutamide.

Self-nanoemulsifying drug delivery system (SNEDDS) improves the oral bioavailability of betulinic acid

Betulinic acid (BA) is a bioactive molecule with antineoplastic, antiviral, anti-inflammatory features; however, it exhibits low solubility in water, which limits its practical applications. Our work aims to develop self-nanoemulsifying drug delivery systems (SNEDDS) to improve the bioavailability of BA. We found that the oil phases containing Lauroglycol FCC and caprylic acid solubilized the greatest amount of the bioactive with 15.8 ± 0.089 and 16.019 ± 0.11 mg/mL, respectively. Pseudoternary phase diagrams were prepared to determine the spontaneous nanoemulsification zone of the systems, using Cremophor EL® and Labrafil M1944CS® as surfactants. Nanoemulsions with particle sizes ranging from approximately ca. 22 to 56 nm and polydispersity indices of 0.058–0.135 were obtained. The SNEDDS were subjected to in vitro gastrointestinal conditions, where the particle size of the nanosystems remained constant up to 105 min of simulated small intestine phase conditions. The in vivo study in a Wistar rat model demonstrated up to a 15-fold increase in BA bioavailability when administered in SNEDDS, compared to free BA.

Lipid-Based Formulations Containing Labrafil M2125-CS: A Deep Investigation on Nanosystem Stability

Labrafil M2125-CS is a non-ionic surfactant component widely used for improving the solubilization of poor water-soluble drugs and as component of lipid-based nanosystem formulation. The aim of this research work was to evaluate in depth the stability of lipid-based nanosystems when exposed at several experimental conditions, such as temperature- and pH-variations, and during a specific storage process—lyophilization. Dynamic light scattering was the main analysis carried out during this research work for investigating eventual physico-chemical variations of nanosystem properties after different storage phases. We demonstrated that many of prepared formulations were able to maintain almost unchanged mean size and polydispersity index values, resisting acid and basic pH or high and low temperature, as well as the freeze-drying process. Finally, the results showed that there are no univocal experimental conditions suitable for the storage of all formulation types, but each sample requires customized conditions.

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.

Oral gel loaded with penciclovir–lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.

Overcoming the dissolution rate, gastrointestinal permeability and oral bioavailability of glimepiride and simvastatin co-delivered in the form of nanosuspension and solid self-nanoemulsifying drug delivery system: A comparative study

Simvastatin (SIM) and glimepiride (GLM) were co-formulated into nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS) to improve their dissolution rate and oral bioavailability. Nanosuspension was prepared by liquid anti-solvent precipitation method, involving supersaturation of a solution by mixing the drug solution in an antisolvent. Liquid SNEDDS were prepared by loading drugs into an isotropic mixture of Capmul MCM, Labrafil M1944CS, Tween-80 and Transcutol P. Both formulations were solidified using spray drying. Enhancement in dissolution rate by 6.4 folds and 4.45 folds was observed for GLM and SIM respectively by preparing their nano-formulations. Drugs’ permeability was also enhanced by loading them into nano-formulations. The pharmacokinetic studies were conducted on rats which revealed increase in oral bioavailability by 6.69- and 4.22-folds for GLM and 1.76- and 2.68-folds for SIM respectively for nanosuspension and solid SNEDDS than their unprocessed forms. Both dissolution rate and oral bioavailability of SIM and GLM got significantly improved through S-SNEDDS and nanosuspension. However, performance of nanosuspension was found better than SNEDDS in terms of dissolution rate and oral bioavailability.

Exploring role of probiotics and Ganoderma lucidum extract powder as solid carriers to solidify liquid self-nanoemulsifying delivery systems loaded with curcumin

Solid self-nanoemulsifying drug delivery system (S-SENDDS) containing Curcumin (CRM) were prepared using combination of Ganoderma lucidum extract powder (GLEP) and probiotics (PB) as carriers. Liquid SNEDDS containing CRM were prepared by mixing Capmul MCM, Labrafil M1944CS, Tween 80 and Transcutol P. These were further spray dried and finally converted into spheroids. The droplet size of reconstituted S-SNEDDS powder and spheroids was found in the range of 35 to 37 nm, zeta potential in the range of - 21.48 to -23.22 mV and drug loading in the range of 95-96%. The release of drug from formulations was found to be more than 90%. Similarly, significant improvement (p < 0.05) in permeability of CRM was observed through SNEDDS using Caco2 cell lines. The non-significant difference (p> 0.05) in drug loading, droplet size, dissolution rate and angle of repose between L-SNEDDS and S-SNEDDS indicated the potential of GLEP-PB to produce stable SNEDDS.

Impact of solidification on micromeritic properties and dissolution rate of self-nanoemulsifying delivery system loaded with docosahexaenoic acid

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of docosahexaenoic acid (DHA) is reported with the aim to achieve enhanced dissolution rate. The optimized composition of liquid SNEDDS (L-SNEDDS) formulation was Labrafil M1944 CS, 47% v/v Tween 80, 27% v/v Transcutol P, and 0.1% v/v DHA. L-SNEDDS were solidified using Syloid XDP 3150 as solid porous carrier. The droplet size, polydispersity index, zeta potential, percentage drug loading, and cloud point for L-SNEDDS were found to be 43.51 ± 1.36 nm, 0.186 ± 0.053, −19.20 ± 1.21 mV, 93.23 ± 1.71, and 88.60 ± 2.54 °C, respectively. Similarly, for solid SNEDDS (S-SNEDDS) the above parameters were found to be 57.32 ± 1.87 nm, 0.261 ± 0.043, −16.60 ± 2.18 mV, 91.23 ± 1.88, and 89.50 ± 1.18 °C, respectively. The formulations (L-SNEDDS, S-SNEDDS powder, and S-SNEDDS tablet) showed significant (p<.05) improvement in dissolution rate of drug in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) as compared to unprocessed DHA. In both the dissolution media, the dissolution rate was found more that 85% in 90 min. Absence of drug precipitation, phase separation, and turbidity during thermodynamic stability studies indicated that the developed SNEDDS were stable. Hence, it was concluded that SNEDDS have offered sufficient stability as well as dissolution rate of DHA.

Self-Microemulsifying Drug Delivery System of Phillygenin: Formulation Development, Characterization and Pharmacokinetic Evaluation.

Phillygenin, as an active ingredient of Forsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin.

Formulation and optimization of microemulsion based sparfloxacin in-situ gel for ocular delivery: In vitro and ex vivo characterization

Conventional eye drops have a major limitation of having short residence time in Cul de sac, which is responsible for low bioavailability of the drug and poor therapeutic response. In-situ gel system having a sol-gel transformation is an attractive approach to increase the drug residence time without compromising the advantage of eye drop of easy application. The present investigation was aimed to prepare microemulsified based in-situ gel system of sparfloxacin to improve its solubility and permeability through the cornea. Labrafil M1944 CS, Acrysol–140 and Transcutol-P were used as lipid, surfactant, and co-surfactant respectively to prepare sparfloxacin containing microemulsion. The design batches prepared according to simplex lattice designs were evaluated for globule size, polydispesity index, pH and drug content. Poloxamer 407, a thermo responsive polymer was used as polymer for preparing in situ gel of optimized formulation which was evaluated for clarity, pH, gelling capacity, and the rheological properties. In addition to that ex-vivo drug permeation and ocular irritation studies were also performed. The prepared optimized formulation was found to be clear, stable and non-irritant after 90 days of storage under accelerated stability condition.

DESARROLLO DE UN SISTEMA DE LIBERACIÓN DE FÁRMACOS AUTO-NANOEMULSIFICANTES (SNEDDS) PARA UN COMPLEJO DE INSULINA CON FOSFATIDILCOLINA MODIFICADA Y POLISACÁRIDOS MUCOADHESIVOS COMO POTENCIAL MEDIO TRATAMIENTO NO INVASIVO CONTRA DIABETES MELLITUS

The present work depicts the development of a SNEDDS system for the administration of insulin, in which an insulin complex was formed with enzymatically modified soy phosphatidylcholine, by means of the solvent elimination technique. In addition, sodium alginate and guar gum were added to this system to provide mucoadherence capacities and to increase insulin protection against gastric conditions. SNEDDS were developed from mixtures of surfactant, co-surfactant and oil phase: Cremophor EL, Labrafil M1944CS and Lauroglycol FCC, respectively: obtaining particle sizes between 27.36-50.53 nm and monomodal distribution. Mucoadhesives were added by orbital agitation and particle sizes between 53.1-83.2 nm were obtained. Finally, nanoemulsions were submitted to an in vitro gastric simulation system, were insulin bioavailability was increased to 46.3% in systems that included mucoadhesive coating. These results show that the developed systems can possibly be used for the administration of insulin by oral route as a potential non-invasive treatment for diabetes.

Formulation and characterization of chlorhexidine HCl nanoemulsion as a promising antibacterial root canal irrigant: in-vitro and ex-vivo studies.

Introduction and aim: Chlorhexidine Hydrochloride [Chx.HCl] has a broad-spectrum antibacterial effect, sustained action and low toxicity so it has been recommended as a potential root canal irrigant. The aim of this study was to improve the penetration ability, cleansing and antibacterial effect of Chx.HCl using a newly formulated Chx.HCl nanoemulsion and use it as root canal irrigant.Methods: Chx.HCl nanoemulsions were prepared using two different oils; Oleic acid and Labrafil M1944CS, two surfactants; Tween 20 and Tween 80 and co-surfactant; Propylene Glycol. Pseudoternary phase diagrams were constructed to designate the optimum systems. The prepared nanoemulsion formulae were evaluated for their drug content, emulsification time, dispersibility, droplet size, in-vitro drug release, thermodynamic stability, In-vitro antibacterial activity and ex-vivo study for the selected formula. Comparisons were made of Chx.HCl nanoemulsion with two different concentrations 0.75% and 1.6% vs Chx.HCl normal particle size as root canal irrigant for their penetration ability, cleansing effect and antibacterial effect.Results: The selected formula was F6 with composition of 2% Labrafil, 12% Tween 80 and 6% Propylene glycol. It has small particle size (12.18 nm), short emulsification time (1.67 seconds), and fast dissolution rate after 2 minutes. It was found to be a thermodynamically/physically stable system. The higher concentration of Chx.HClnanoemulsion1.6% shows the best penetration ability compared to Chx.HCl normal particle size due to the smaller particle size. Chx.HCl nanoemulsion 1.6% has the lowest mean value of the remaining debris surface area (2001.47 µm2) when compared to normal particle size material (2609.56 µm2).Conclusion: Chx.HCl nanoemulsion preparation has better cleansing ability and antibacterial effect with high efficacy on Enterococcus faecalis, where high reduction rate or complete eradication of bacterial cells has been achieved.

Coadministration of Polypeptide-k and Curcumin Through Solid Self-Nanoemulsifying Drug Delivery System for Better Therapeutic Effect Against Diabetes Mellitus: Formulation, Optimization, Biopharmaceutical Characterization, and Pharmacodynamic Assessment.

An attempt has been made to prepare solid self-nanoemulsifying drug delivery system (SNEDDS) of polypeptide-k (PPK) and curcumin (CRM) using Labrafil M1944 CS as oil, Tween-80 as surfactant, Transcutol P as cosurfactant and Aerosil-200 (A-200) as porous hydrophobic carrier for improving their antidiabetic potential through oral delivery. Box-Behnken Design was used to optimize the liquid formulation based on the results of the mean droplet size, polydispersity index, percentage drug loading, and zeta potential. The formulation was adsorbed on Aerosil-200 through spray drying. The formulation showed desirable micromeritic, disintegration, and dissolution properties. About fivefold rise in the dissolution and permeation rate for drugs was observed from formulations vis a vis their unprocessed forms. The formulation was found to be stable with variation in pH, dilution, and temperature. The individual solid SNEDDS formulation of PPK and CRM and their combination were evaluated for antidiabetic potential and the results were compared with their naive forms on streptozotocin-induced diabetic rats. The results revealed better control of serum glucose level and other biochemical tests, such as liver parameters, lipid profiles, and antioxidant levels, as well as histological evaluation of pancreatic tissues in all the solid SNEDDS formulation as compared with their naive forms.

Enhanced Chemical Stability of Hirsutenone Incorporated into a Nanostructured Lipid Carrier Formulation Containing Antioxidants

To enhance the chemical stability of hirsutenone (HST), a natural diarylheptanoid, nanostructured lipid carrier (NLC) formulations containing antioxidants were employed. The stability and shelf‐life of HST‐containing formulations were assessed by using accelerated aging tests. Drug‐free NLC formulations, using Compritol 888 ATO as a solid lipid, Labrafil M1944 CS as an oil, and Tween 80 as a surfactant, had a particle size of approximately 177 nm, a polydispersity index of 0.257, and a zeta potential of −15.5 mV. Drug‐ or antioxidant‐loading slightly increased the particle size but did not alter the surface charge of the NLC formulations. HST entrapment efficiencies were 86.83% and 88.19% for antioxidant‐free and antioxidant‐added NLC formulations, respectively. NLC formulations extended the half‐life of HST relative to aqueous solutions, but the stabilizing effect was unsatisfactory. The use of 1% ascorbyl palmitate (AP) and 1% ethylenediaminetetraacetic acid (EDTA) in the NLC formulations resulted in the greatest stabilization of HST, with a half‐life of approximately 120 days at 40°C. The stability assessments of different NLC formulations were conducted based on the first‐order kinetics and the shelf‐life at different temperatures was estimated by using the Q10 method. Assuming a Q10 value of 2, the shelf‐life of AP/EDTA‐added NLC formulations at 25°C and 4 °C was 51.2 and 219.5 days, respectively. Although the HST stability was considerably enhanced by NLC formulation and further improved by adding antioxidants, alternative studies to assure the sufficient stability and enable the practical application of NLC formulations in product development are still required.

Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation

This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.