Tocopherol Polyethylene Glycol Succinate Research Articles

The potential modulatory impact of garlic-selenium nanoparticles coated with synthetic tocopherol polyethylene glycol-succinate against lead acetate toxicity in male rabbits

Toxic heavy metal lead enters in the environment due to industrial and anthropogenic activity threatens ecosystems and public health. Natural garlic extract (GE) exhibits antioxidant properties and various applications against several ailments. Therefore, this study scrutinized the protective effects of tocopherol polyethylene glycol succinate-coated garlic selenium (TPGS-GSNP) against lead acetate (LA) toxicity in rabbits. Sixty-four mature male rabbits were involved and divided into 8 equal groups. They received distilled water (negative control; T1), 30 mg/kg bw of LA (positive control; T2), 800 mg/kg bw of GE (T3), GE + LA (T4), 1 mg/kg bw of TPGS-Selenium (T5), TPGS-S + LA (T6), 1 mg/kg bw of TPGS-GSNP (T7), and TPGS-GSNP + LA (T8). Consequently, treatments were administered three times a week for 12 weeks. Following the treatment period, serum oxidant-antioxidant, protein, and lipid profiles, liver and kidney function, histopathological findings of the adrenal, liver, and kidneys, femur bone marrow chromosomal aberrations, and mitotic activity were collected and analysed. LA exposure showed significant reductions in antioxidant levels, organ weights, and mitotic activity while increasing oxidative stress, corticosteroid levels, and chromosomal aberrations. Importantly, TPGS-GSNP administration significantly improved these markers compared to the LA group. In addition, histological analysis revealed structural improvements of the studied organs in the TPGS-GSNP group compared to the LA group, which displayed high cellular necrotic and degenerative changes. In conclusion, synthetic TPGS-GSNP demonstrated higher protective efficacy against LA-induced toxicity compared to natural GE or selenium alone. However, more future studies could be conducted to explore the potential of TPGS-GSNP as an anticancer or immunomodulatory agent.

Preparation of Naringenin Nanosuspension and Its Antitussive and Expectorant Effects.

Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical therapeutic effect of NRG is limited by its low bioavailability due to poor solubility. To enhance the solubility, naringenin nanosuspensions (NRG-NSps) were prepared by applying tocopherol polyethylene glycol succinate (TPGS) as the nanocarrier via the media-milling method. The particle size, morphology, and drug-loading content of NRG-NSps were examined, and the stability was evaluated by detecting particle size changes in different physiological media. NRG-NSps exhibited a flaky appearance with a mean diameter of 216.9 nm, and the drug-loading content was 66.7%. NRG-NSps exhibited good storage stability and media stability. NRG-NSps presented a sustainable release profile, and the cumulative drug-release rate approached approximately 95% within 7 d. NRG-NSps improved the antitussive effect significantly compared with the original NRG, the cough frequency was decreased from 22 to 15 times, and the cough incubation period was prolonged from 85.3 to 121.6 s. Besides, NRG-NSps also enhanced expectorant effects significantly, and phenol red secretion was increased from 1.02 to 1.45 μg/mL. These results indicate that NRG-NSps could enhance the bioavailability of NRG significantly and possess a potential clinical application.

Honokiol Prodrug Nanoparticles Based on In Situ Albumin Binding for Long Circulation and High Tumor Uptake.

Honokiol (HK) has antiproliferation effects against numerous cancer cells, but its low solubility and bioavailability impede its application. In this study, a prodrug of HK (HP) featuring a maleimide group was synthesized and then mixed with tocopherol polyethylene glycol succinate to prepare prodrug nanoparticles (HP-NPs). In vitro albumin binding experiments showed that HP rapidly reacted with the cysteine thiols of albumin to form a covalent conjugate that released HK slowly in the LLC tumor cell line. In vitro cell apoptosis and uptake assays showed that the cellular uptake of the HK increased into the LLC cells as the albumin concentration increased. Strikingly, in vivo pharmacokinetics and pharmacodynamics measurements demonstrated that the HP-NPs significantly prolonged the circulation and increased tumor accumulation. Taken together, our study demonstrated, both in vitro and in vivo, that the albumin-based HP-NPs delivery system holds significant potential toward the treatment of lung cancer in clinical studies.

Self‐Assembly of Cholesterol‐Doxorubicin and TPGS into Prodrug‐Based Nanoparticles with Enhanced Cellular Uptake and Lysosome‐Dependent Pathway in Breast Cancer Cells

AbstractDeveloping new easy‐to‐prepare functional drug delivery nanosystems with good storage stability, low hemotoxicity, as well as controllable drug delivery property, has attracted great attention in recent years. In this work, a cholesterol‐based prodrug nanodelivery system is prepared by self‐assembly of cholesterol‐doxorubicin prodrug conjugates (Chol‐Dox) and tocopherol polyethylene glycol succinate (TPGS) using thin‐film hydration method. The Chol‐Dox/TPGS assemblies (molar ratio 2:1, 1:1, and 1:2) are able to form nanoparticles with average hydrodynamic diameter of ≈140–214 nm, surface zeta potentials of ≈−24.2–−0.3 mV, and remarkable solution stability in 0.1 m PBS, 16 days). The Chol‐Dox/TPGS assemblies show low hemotoxicity and different cytotoxicity profiles in breast cancer cells (MCF‐7 and MDA‐MB‐231), which are largely dependent on the molar ratio of Chol‐Dox and TPGS. The Chol‐Dox/TPGS assemblies tend to enter into MCF‐7 and MDA‐MB‐231 cells through non‐Clathrin‐mediated multiple endocytosis and lysosome‐dependent uptake pathways, moreover, these nanoassemblies demonstrate lysosome‐dependent intracellular localization, which is different from that of free DOX (nuclear localization). The results demonstrate that the Chol‐Dox/TPGS assemblies are promising cholesterol‐based prodrug nanomaterials for breast cancer chemotherapy.Practical Applications: This work demonstrates a lipid prodrug‐based nanotherapeutic system. Herein the Chol‐Dox/TPGS nanoassemblies could serve as promising and controllable cholesterol‐based prodrug nanomaterials/nano‐formulations for potential breast cancer chemotherapy.

Nanosuspension coated multiparticulates for controlled delivery of albendazole

Objective Improving solubility and bioavailability of albendazole (ALB). Significance ALB is a broad-spectrum anthelminthic BCS class II drug with aqueous solubility of solubility of 4.1 mg/l at 25 °C and oral bioavailability of <5%. Methods ALB nanosuspensions (NSs) were prepared by evaporative antisolvent precipitation using tocopherol polyethylene glycol succinate (TPGS) and polyvinyl pyrrolidone (PVP) as stabilizers and characterized for particle size, polydispersity index, and zeta potential. 32 factorial design was used to investigate effect of stabilizer concentration and speed of stirring on particle size. Concentration of TPGS was varied from 0.03 to 0.05% w/v and PVP K-30 was constant at 0.04% w/v. Stirring speed range was 1000–3000 rpm. Optimized NS was loaded on Espheres and coated with Eudragit S10& L100 and studied for friability, surface morphology and release kinetics. Results Factorial experiments revealed pronounced effect of TPGS on particle size. Optimized batch had particle size of 251 ± 7.2 nm and zeta potential −16.2 ± 2.68 mV. Saturation solubility showed increase of 16-fold in water whereas in phosphate buffer increase was fourfold. ALB-NS secondary coated Espheres released 94.3% drug in 10 h whereas ALB-MS (microsuspension) coated Espheres showed 58% release. A 1.3-fold increase in AUC0-10h was evident. Permeation from ALB-NS coated Espheres was 32% in 60 min while for ALB-MS coated Espheres it was 20%. Permeation increase occurred due to presence of TPGS which acts as a permeation enhancer.

DEVELOPMENT AND CHARACTERIZATION OF NEVIRAPINE LOADED AMORPHOUS SOLID DISPERSIONS FOR SOLUBILITY ENHANCEMENT

Objective: The present study entails the development of nevirapine (NVP)-loaded solid dispersions for improvement of solubility and in vitro profile.&#x0D; Methods: Solid dispersions were prepared through blending with a hydrophilic polymer and Vitamin E tocopherol polyethylene glycol succinate (TPGS) using the solvent evaporation method. The optimized formulations were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and morphological investigations by scanning electron microscopy. The optimized formulation was converted into fast dissolving tablets (FDTs) through direct compression technique and was characterized for pre- and post-compression parameters. Both amorphous dispersions and FDTs were evaluated for in vitro drug release.&#x0D; Results: NVP showed pH-dependent solubility in different pH media. Above 0.002% w/v Vitamin E TPGS, a linear relationship was observed between the NVP solubility and Vitamin E TPGS concentration. According to the study, the most suitable formulation was NVP:Vitamin E TPGS (1:0.75) in 30 ml solvent with a drug release of 82.96% in 2 h. The analysis of dissolution data of optimized formulation indicated the best fitting with the Higuchi model. FDTs exhibited faster drug release of about 50% in 5 min indicating desired attributes for the immediate dosage form.&#x0D; Conclusion: The present study vouches for better in vitro profile of NVP from solid dispersion based FDTs.

Silodosin oral films: Development, physico-mechanical properties and in vitro dissolution studies in simulated saliva

Sublingual film dosage forms for drugs used for fast symptomatic treatment have promise because they allow a rapid onset of action. The aim of this study was to prepare films of silodosin intended for sublingual administration for the symptomatic treatment of benign prostatic hyperplasia in men. Hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were used as film-forming polymers. The effects of the polymers and the surfactant tocopherol polyethylene glycol succinate (TPGS) on the physico-mechanical properties and dissolution behavior of the films in simulated saliva were investigated. The eight silodosin oral films developed (F1–F8) contained 8 mg silodosin per 6 cm2 film and HPMC or HPMC-AS in drug:polymer ratios of 1:5 or 1:3, while four also contained TPGS (0.5% w/w). The films were characterized using DSC, TGA, SEM, and PXRD and the mechanical properties were investigated by measuring tensile strength, elongation at break and Young's modulus. The mechanical properties of the films were dependent on the ratio of polymer used. The in vitro dissolution and drug release studies indicated that HPMC-AS films disintegrated more quickly than HPMC films. Silodosin was shown to be dispersed within the polymers. Despite silodosin being submicronized in the HPMC films, the dissolution and drug release rate (time for 80% release) from HPMC films was significantly faster than from HPMC-AS films. TPGS increased the drug release rate to a greater extent with HPMC than with HPMC-AS. The degree of saturation of formulation F4 was >1, which shows potential for improving oral absorption of silodosin.

Novel Antimicrobial Topical Gel That Exhibits Inhibitory Effectiveness Toward Common Microbes in Wound Infection (P19-007-19)

ObjectivesThis research project focused on the inhibitory effectiveness of a novel antimicrobial gel (AMG) towards a panel of common microbes involved in wound infections. MethodsA novel antimicrobial topical gel consisting of vitamin E TPGS (tocopherol polyethylene glycol succinate), ascorbyl palmitate, zinc aspartate, lavender oil and deionized distilled water was developed in our laboratory. Various in vitro techniques were used to determine the effectiveness of AMG on prokaryotic and eukaryotic microbes. ResultsIn vitro experiments show that while AMG had varying inhibitory effects on both prokaryotic and eukaryotic microbes, there was a predilection for AMG to inhibit planktonic growth and biofilm formation of Staphylococcus species, most notably Methicillin Resistant Staphylococcus aureus (MRSA). The inhibitory effect of the AMK on planktonic growth was immediate with a four-fold reduction in growth, compared to controls, within 4 to 6 hrs of induction. Within 24 hrs S. aureus growth was minimal and complete inhibition of growth was achieved within 48 hrs. In an in vitro biofilm model, the AMG inhibited Staphylococcus biofilm attachment by 67% (density), 82% (mass) and 95% (viability). On pre-formed established biofilms, the AMG was able to inhibit 47% (density), 47% (mass) and 44% (viability) Staphylococcus biofilms. Antibiotic comparison experiments demonstrated that the MIC (minimum inhibitory concentration) of Mupirocin was <1% while the AMG was slightly elevated at <2%. However, thus far, Staphylococcus has not demonstrated resistance to AMG whereas it has become a troubling concern for Mupirocin. Fluorescent microscopy using LIVE/DEAD (SYTO9/propidium iodide) staining of Staphylococcus culture controls exhibited robust growth and viability while AMG treated Staphylococcus cultures showed sparse growth of non-viable cells. AMG has inhibitory activities against normal and methicillin resistant S. pseudintermedius which are prevalent in lick granulomas in canines. ConclusionsAMG is nontoxic to humans and canines and demonstrates potential for use in wound infections as an alternative to commonly prescribed antibiotics without the unintended drug resistance seen with antibiotics. AMG is an effective treatment option, this far in vitro, for Staphylococcus infections that are particularly prone to biofilm growth. Funding SourcesETSU, Honors College, Student/Faculty Collaborative Research Grant.

Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine.

Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with β-CD, HP-β-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10-13-folds higher with ternary complexes in distilled water and 12-14-fold higher in 0.1N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within β-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.

Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension

Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α–tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts. CoQ10/TPGS showed a significant neuroprotective effect compared to control with DARC (p<0.05) and Brn3 (p<0.01). Topical CoQ10 appears an effective therapy preventing RGC apoptosis and loss in glaucoma-related models.

Intravenous Delivery of Xenon Incorporated in Thermosensitive Nano-Emulsions for Anesthesia.

Xenon anesthesia has several advantages over conventional anesthetics, however, it has not been widely used in clinical sites, since the cost and minimum alveolar concentration were higher than conventional inhalational anesthetics. The purpose of this study was to develop an optimum vehicle for stable intravenous delivery of xenon with sufficient concentration. Thermosensitive lipid based nano-emulsions (TS-LE) were prepared by blending medium chain triglyceride, polyethylene glycol-15-hydroxystearate, D-α tocopherol polyethylene glycol succinate and Poloxamer 188. Three folds higher xenon was loaded in TS-LE when it was prepared under 5.5 atm of xenon pressure compared to that under 1 atm of xenon pressure at 22 °C (11.4±0.7 vs. 3.82±0.34 mg/ml). Poloxamer 188 conferred thermosensitive viscosity and outer rigid structure on TS-LE, and the properties led to the enhanced stability of xenon compared to usual lipid emulsion. Induction of anesthesia was investigated by monitoring loss of forepaw righting reflex (LORR) in rats. The ED50 for LORR was 131.9 mg/kg and the anesthesia was maintained for 65.3±7.1 sec at a dose of 179 mg/kg in rats. When it is considered that TS-LE stably loads enough concentration of xenon for the induction of therapeutically sufficient anesthesia, TS-LE may be regarded as a promising candidate for intravenous xenon delivery.

An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant

Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (∼37°C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed.

Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery.

The objective of this study was to develop a clear, aqueous rapamycin-loaded mixed nanomicellar formulations (MNFs) for the back-of-the-eye delivery. MNF of rapamycin (0.2%) was prepared with vitamin E tocopherol polyethylene glycol succinate (TPGS) (Vit E TPGS) and octoxynol-40 (Oc-40) as polymeric matrix. MNF was characterized by various parameters such as size, charge, shape, and viscosity. Proton nuclear magnetic resonance ((1)H NMR) was used to identify unentrapped rapamycin in MNF. Cytotoxicity was evaluated in human retinal pigment epithelial (D407) and rabbit primary corneal epithelial cells (rPCECs). In vivo posterior ocular rapamycin distribution studies were conducted in male New Zealand white rabbits. The optimized MNF has excellent rapamycin entrapment and loading efficiency. The average size of MNF was 10.98 ± 0.089 and 10.84 ± 0.11 nm for blank and rapamycin-loaded MNF, respectively. TEM analysis revealed that nanomicelles are spherical in shape. Absence of free rapamycin in the MNF was confirmed by (1)H NMR studies. Neither placebo nor rapamycin-loaded MNF produced cytotoxicity on D407 and rPCECs indicating formulations are tolerable. In vivo studies demonstrated a very high rapamycin concentration in retina-choroid (362.35 ± 56.17 ng/g tissue). No drug was identified in the vitreous humor indicating the sequestration of rapamycin in lipoidal retinal tissues. In summary, a clear, aqueous MNF comprising of Vit E TPGS and Oc-40 loaded with rapamycin was successfully developed. Back-of-the-eye tissue distribution studies demonstrated a very high rapamycin levels in retina-choroid (place of drug action) with a negligible drug partitioning into vitreous humor.

Surface modification of sepiolite nanofibers with PEG based compounds to prepare polymer electrolytes

The controlled surface modification of the fibrous clay mineral, sepiolite (Sep), with poly(ethylene glycol) (PEG) and Vitamin E tocopherol polyethylene glycol succinate (TPGS) is presented in this work. Sep, which has a rich surface reactivity because of the presence of silanol groups on its surface, is employed as nanofiller in clay polymer nanocomposites (CPN). It organizes itself into bundles of nanofibers which are difficult to separate from one another unless aqueous gels are prepared under very specific conditions. In the form of an aqueous gel, however, separation of the nanofibers and chemical modification of their surface can be easily done. Sets of very different organosepiolites (OSep) can be obtained in this way. In this work the resulting OSep are characterized in terms of mass incorporation and yields of reaction, specific surface, surface texture, surface water content and thermal stability. As the final purpose of these OSep is the mechanical reinforcement of poly(ethylene oxide) (PEO) based electrolytes highly loaded with ethylene carbonate (EC), blends with PEG or PEO and lithium triflate, with or without EC are prepared and the properties of the final materials are found to be strongly dependent on the type of OSep employed. In particular, examples on the fillers dispersion in the PEO nanocomposites and on their stability in dispersion of PEG/EC blends are described.

Combinational Delivery of Hydrophobic and Hydrophilic Anticancer Drugs in Single Nanoemulsions To Treat MDR in Cancer

In this study, we developed the core-matched nanoemulsions (NEs) functionalized by vitamin E (VE) and tocopherol poly(ethylene glycol)succinate (TPGS) to codeliver hydrophobic and hydrophilic drugs, paclitaxel (PTX) and 5-fluoroucacil (5-FU), in order to achieve synergistic effects and overcome PTX resistance in a multi-drug-resistant (MDR) human epidermal carcinoma cell line KB-8-5. Antitumor effect of the combination therapy based on core-matched technology (CMT) was evaluated in vitro and in vivo in mice. The core-matched NEs showed entrapment efficiency of >90% and were of nanoscale particle size and negative zeta-potential. The combined core-matched NEs exhibited concentration and time-dependent cytotoxicity against PTX-sensitive KB-3-1 cells and PTX-resistant KB-8-5 cells as well as an obviously increased G2/M phase block. The improvements in therapeutic response over either PTX–VE or 5-FU–TPGS therapy alone were demonstrated by the ability to effectively induce the apoptosis of tumor cells via up-regulation of tumor suppressor p53 and β-tubulin and by the significant inhibition of cell cycle progression. The combination therapy led to dramatic inhibition of tumor growth with little toxicity in vivo, especially in the PTX-resistant KB-8-5 tumors, whereas Taxol had little therapeutic effect. This was mainly ascribed to the synergism of PTX and 5-FU and the reverse of MDR by the inhibition of ATPase activity by VE and TPGS. Coencapsulation of two chemotherapeutic agents with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and low toxicity. The CMT markedly facilitated the long circulation of PTX and 5-FU, which was closely associated with the high accumulation of chemotherapeutic agents within the tumors and the improvement of antitumor efficacy. The current study demonstrated the feasibility of incorporating PTX and 5-FU targeting to different pathways into a single core-matched NE for the reversal of MDR and synergism in cancer therapy.

Determination of Required HLB of Capryol 90

The required hydrophilic-lipophilic balance (HLB) of an oily substance indicates the HLB of the surfactants required to prepare a stable emulsion using the oil. This study utilizes empirical method to calculate required HLB (RHLB) of Capryol 90 using surfactant blends (Span 20, Tween 20, vitamin E TPGS, Pluronic F68, Span 60, and Tween 80). The methods used were assessment of degree of creaming after centrifugation and after shelf storage for 28 days at room temperature, turbidimetric method, accelerated stability study, and droplet size analysis. The droplet size was found to be in the range of 15 to 2 µm and v/v% separation after centrifugation was found to be 0–82%. The RHLB for Capryol 90 was found to be 15. The effect of various surfactant blends was investigated. Results revealed that a blend of tocopherol polyethylene glycol succinate (TPGS) and Pluronic F68 gave the most stable emulsion for Capryol 90.

Spray‐Dried Redispersible Emulsion to Improve Oral Bioavailability of Itraconazole

AbstractDry emulsions are powdery, lipid‐based formulations from which an o/w‐emulsion can be easily reconstituted in vivo or when exposed to water. The objective of this work was to prepare and characterize dry emulsion of itraconazole (ITZ) to improve its solubility and bioavailability. Dry emulsions were prepared by spray‐drying liquid o/w‐emulsions containing carriers like maltodextrin, sucrose, and lactose. Propylene glycol monocaprylate was selected as oil phase, and surfactant blends of vitamin E tocopherol polyethylene glycol succinate and triblock PEO–PPO–PEO copolymer as emulsifying agents. Several oil:water and carrier:water ratios were tested. An optimum formulation was selected using 32 full factorial design. The droplet size, rheological behavior, and drug release from o/w‐emulsion before and after reconstitution and the micromeritic properties of spray‐dried product were investigated. Maltodextrin was used as a carrier for preparing dry emulsions. The optimized dry emulsion was characterized using DSC, SEM, PXRD, and in vivo study. The SEM analysis showed that dry emulsion consisted of well‐separated particles with smooth surfaces. The DSC and XRD study showed that ITZ in the dry emulsion is in the molecular dispersion state. Globule size analysis showed that dry emulsion had good reconstitution properties. The emulsions were found to be thermodynamically stable when subjected to cyclical freeze–thaw cycles and centrifugation tests. The average globule size of emulsions ranged from 0.994 to 1.668 μm. A 71.35 % increase in Cmax and 114.78 % increase in AUC was evident for ITZ dry emulsion as compared to plain ITZ.

Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu

The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co-solvent- and cyclodextrin-based approaches. Different combinations of co-solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-β-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague–Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar.

Self-nanoemulsifying drug delivery system of cefpodoxime proxetil containing tocopherol polyethylene glycol succinate

Context: Lipid based drug delivery systems have gained prominence in last decade for drugs with dissolution rate limited oral bioavailability.Objective: To improve the solubility, permeability and oral bioavailability of cefpodoxime proxetil, β-lactam antibiotic. It is BCS Class IV drug having solubility 400 µg/mL and 50% oral bioavailability.Materials and methods: Self-nanoemulsifying drug delivery system (SNEDDS) using various surfactant and cosurfactants such as tween 80, tocopheryl polyethylene glycol succinate (TPGS), propylene glycol and Capmul MCM as oil phase were prepared. Ternary phase diagrams were constructed to identify stable microemulsion region. Percent transmittance studies helped to shortlist the surfactant–cosurfactant combination.Results and discussion: Tween 80 and TPGS as surfactants and Capmul MCM as oil phase were found to produce stable nanoemulsions. Five formulations of SNEDDS had globule size of 55–60 nm and zeta potential of −4 to −11 mV. Self-emulsification time was between 221 and 370 s, while viscosity was dependent on composition of SNEDDS. Cloud point was above 70°C which indicated the retention of in vivo self-emulsifying properties. Average flux for cefpodoxime proxetil (CP) and SNEDDS was 0.104 and 0.985 µg/cm2 min. Permeability was 19.72 and 206 for CP and SNEDDS. Liquid SNEDDS spray coated onto micropellets of microcrystalline cellulose (18–20#) were analysed by scanning electron microscope (SEM), self-emulsification and in vitro dissolution. A 5.36-fold increase in area under curve AUC0–∞ was observed for CP-SNEDDS than plain drug. Minimum inhibitory concentration (MIC) was lower for SNEDDS. Liquid and SNEDDS micropellets were stable under accelerated conditions.Conclusion: SNEDDS formulations led to improved oral bioavailability due to enhanced solubilization of selected drug.

Self-Assembled Biodegradable Nanoparticles Developed by Direct Dialysis for the Delivery of Paclitaxel

The main objective of this study was to obtain self-assembled biodegradable nanoparticles by a direct dialysis method for the delivery of anticancer drug. The in vitro cellular particle uptake and cytotoxicity to C6 glioma cell line were investigated. Self-assembled anticancer drugs--paclitaxel-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLA) nanoparticles--were achieved by direct dialysis. The physical and chemical properties of nanoparticles were characterized by various state-of-the-art techniques. The encapsulation efficiency and in vitro release profile were measured by high-performance liquid chromatography. Particle cellular uptake was studied using confocal microscopy, microplate reader, and flow cytometry. In addition, the cytotoxicity of this drug delivery system was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C6 glioma cell line to predict the possible dose response of paclitaxel-loaded PLGA and PLA nanoparticles. PLGA and PLA nanoparticles with or without vitamin E tocopherol polyethylene glycol succinate (TPGS) as an additive were obtained, in which the sustained release of paclitaxel of more than 20 days was achieved. The coumarin6-loaded PLGA and PLA nanoparticles could penetrate the C6 glioma cell membrane and be internalized. The cytotoxicity of paclitaxel-loaded nanoparticles seemed to be higher than that of commercial Taxol after 3 days incubation when paclitaxel concentrations were 10 and 20 microg/ml. Direct dialysis could be employed to achieve paclitaxel-loaded PLGA and PLA nanoparticles, which could be internalized by C6 glioma cells and enhance the cytotoxicity of paclitaxel because of its penetration to the cytoplasm and sustained release property.