Eudragit E100 Research Articles

Preparation and Characterization of Electrospun Ketoconazole Loaded Nanofibers as Dermal Patch

Objective: This study aims to formulate a ketoconazole patch containing electrospun nanofibres and enhance the solubility due to theincreased particle surface using the electrospinning method. Methods: The Design-Expert version13 software was used in experimental designing, to ensure an efficient nanofiber preparation process. Several nanofiber formulations were prepared with different concentrations of drug and polymers. In this study, Ketoconazole was selected as the model drug, ketoconazole is widely used as an antifungal drug in the treatment of fungal infections. Eudragit and Polyethylene glycol polymers were used with ketoconazole to formulate electrospun nanofibers. Then Ketoconazole nanofibers were investigated and evaluated chemically and morphologically by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Results: Utilizing the electrospinning method, Ketoconazole electrospun nanofiber was successfully fabricated. The producedketoconazole-loaded nanofibers mat was formulated as a dermal patch. The Eudragit and polyethylene glycol polymers revealed goodcharacteristics that led to the production of uniform ketoconazole nanofibers. The prepared patch showed good physical and mechanicalproperties. The SEM results Images for the produced nanofiber mat showed good nanofiber distribution and no beads formation withseveral fiber diameter sizes, while Fourier Transform Infrared Spectroscopy findings revealed the conjugation between polymers andketoconazole pure powder, the major characteristic peaks of ketoconazole appeared in the FTIR spectrum. Formula 7 showed minimumnanofibers diameter with maximum entrapment efficiency. Conclusions: In this study, the use of the electrospinning method completed the formulation of a dermal patch containing antifungalnanofibers successfully. Using design expert software to ensure maximum optimization, two biocompatible polymers were used, Eudragit E100 and PEG 600 to formulate ketoconazole nanofibers. The formulated dermal patch could be promising for pharmaceutical antifungal applications.

Formulation and In-Vitro Penetration Test of Ketoprofen Patch with Addition Aloe vera Powder (Aloe vera L.) Bioenhancer

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) which is generally used to reduce pain and inflammation. The main obstacle in administering drugs via transdermal is the low penetration of drugs through the skin. Aloe vera contains lignin compounds which are thought to be bioenhancer. This research aims to formulate ketoprofen and aloe vera powder in form patch and compare penetration patch with and without the addition of aloe vera powder. Preparation patch 3 formulas were made with different ratios of HPMC E5 and Eudragit E100 polymers F1 (6:2), F2 (8:2), F3 (10:2). Formula 3 is the best formula with a comparison of HPMC E5 and Eudragit E 100 of 10:2. Formula 3 has a thin, dry patch and is easy to remove from the mold. F3 then remade with additions bioenhancer by 5 % and patch without additions bioenhancer. The results of the physical quality test showed that the formula with and without the addition of aloe vera as an enhancer has uniform weight, thickness, pH and folding resistance which meets the requirements for patch preparation. Franz diffusion cell result for patch preparations with the addition of aloe vera showed a better penetration value than without the addition of aloe vera with a cumulative value of 92.5815 μg/cm2 and a total flux of 260.4355 μg/cm2 hour.

Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches.

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles.

On-Demand Sequential Release of Dual Drug from pH-Responsive Electrospun Janus Nanofiber Membranes toward Wound Healing and Infection Control.

Drugs against bacteria and abnormal cells, such as antibiotics and anticancer drugs, may save human lives. However, drug resistance is becoming more common in the clinical world. Nowadays, a synergistic action of multiple bioactive compounds and their combination with smart nanoplatforms has been considered an alternative therapeutic strategy to fight drug resistance in multidrug-resistant cancers and microorganisms. The present study reports a one-step fabrication of innovative pH-responsive Janus nanofibers loaded with two active compounds, each in separate polymer compartments for synergistic combination therapy. By dissolving one of the compartments from the nanofibers, we could clearly demonstrate a highly yielded anisotropic Janus structure with two faces by scanning electron microscopy (SEM) analysis. To better understand the distinctive attributes of Janus nanofibers, several analytical methods, such as X-ray diffraction (XRD), FTIR spectroscopy, and contact angle goniometry, were utilized to examine and compare them to those of monolithic nanofibers. Furthermore, a drug release test was conducted in pH 7.4 and 6.0 media since the properties of Janus nanofibers correlate significantly with different environmental pH levels. This resulted in the on-demand sequential codelivery of octenidine (OCT) and curcumin (CUR) to the corresponding pH stimulus. Accordingly, the antibacterial properties of Janus fibers against Escherichia coli and Staphylococcus aureus, tested in a suspension test, were pH-dependent, i.e., greater in pH 6 due to the synergistic action of two active compounds, and Eudragit E100 (EE), and highly satisfactory. The biocompatibility of the Janus fibers was confirmed in selected tests.

DEVELOPMENT OF CASTICIN-LOADED ETHYL CELLULOSE MICROPARTICLES BY SOLVENT EVAPORATION METHOD WITH SINGLE EMULSION SYSTEM

Objective: Casticin (Vitexicarpin) has shown immunoregulatory, antitumor, cytotoxicity, anti-inflammatory and analgesic properties. Application of the valuable bioactive compounds can be limited by their unpleasant taste, low bioavailability, volatilization of active compounds, sensitivity to the temperature, oxidation and UV light, as well as in vivo instability. The problem can be solved by coating the Casticin with a microencapsulation technique. The purpose of this research was to formulate the microcapsules of Casticin with solvent evaporation technique using Ethocel 10 cP. Methods: The microencapsulation process of Casticin was done by solvent evaporation technique (O/W: oil in water). The formula of Casticin microcapsules were designed into three formulas (Ethocel 10 cP: 10%, 15% and 20%). Microcapsules of Casticin were characterized for particle size, in terms of surface morphology by scanning electron microscope (SEM), encapsulation efficiency and release test. Results: In this research, the micoparticles containing Casticin has been developed by using ethyl cellulose (Ethocel 10 cP) as the polymer matrix. The results showed that high concentration of polymer (Ethocel 10 cP) used in microencapsulation resulted in better Casticin microcapsules in terms of physical characteristics. Particle size of microcapsules containing Casticin were in the range of 42.51 to 61.47 μm. Encapsulation efficiency (% EE) was categorized as good because the value were ≥ 80% to, which 91.57% to 96.24%. SEM picture of Casticin microcapsules revealed that the surface of microcapsule were a smooth surface and no pores of microcapsule were obtained. When Eudragit E100 used as a polymer, a rough and porous surface of microcapsule were obtained. Conclusion: It can be concluded that microcapsules of Casticin can be prepared by solvent evaporation method with a single emulsion system (O/W) using Ethocel 10 cP as polymer. Characterization of the microcapsules revealed that ethyl cellulose used on this method is applicable to produce microcapsules which stable in physical properties. A higher polymer concentration led to a more viscous solution, which delayed the polymer precipitation and resulted in a less porous polymer matrix with a slower drug release.

Cytocompatibility, antibacterial, and corrosion properties of chitosan/polymethacrylates and chitosan/poly(4-vinylpyridine) smart coatings, electrophoretically deposited on nanosilver-decorated titania nanotubes.

The development of novel implants subjected to surface modification to achieve high osteointegration properties at simultaneous antimicrobial activity is a highly current problem. This study involved different surface treatments of titanium surface, mainly by electrochemical oxidation to produce a nanotubular oxide layer (TNTs), a subsequent electrochemical reduction of silver nitrate and decoration of a nanotubular surface with silver nanoparticles (AgNPs), and finally electrophoretic deposition (EPD) of a composite of chitosan (CS) and either polymethacrylate-based copolymer Eudragit E 100 (EE100) or poly(4-vinylpyridine) (P4VP) coating. The effects of each stage of this multi-step modification were examined in terms of morphology, roughness, wettability, corrosion resistance, coating-substrate adhesion, antibacterial properties, and osteoblast cell adhesion and proliferation. The results showed that the titanium surface formed nanotubes (inner diameter of 97 ± 12 nm, length of 342 ± 36 nm) subsequently covered with silver nanoparticles (with a diameter of 88 ± 8 nm). Further, the silver-decorated nanotubes were tightly coated with biopolymer films. Most of the applied modifications increased both the roughness and the surface contact angle of the samples. The deposition of biopolymer coatings resulted in reduced burst release of silver. The coated samples revealed potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. Total elimination (99.9%) of E. coli was recorded for a sample with CS/P4VP coating. Cytotoxicity results using hFOB 1.19, a human osteoblast cell line, showed that after 3 days the tested modifications did not affect the cellular growth according to the titanium control. The proposed innovative multilayer antibacterial coatings can be successful for titanium implants as effective postoperative anti-inflammation protection.

Development of taste-masking microcapsules containing azithromycin by fluid bed coating for powder for suspension and in vivo evaluation

This research aims to develop bitter taste-masking microcapsules containing azithromycin (AZI) by a simpler and familiar method, fluid-bed coating technology, in comparison with Zithromax®. Cores of microcapsules, AZI microparticles, were prepared by fluid-bed granulation, then taste-masking polymer was covered on by fluid-bed coating technique. Eudragit L100, Eudragit RL100, and ethyl cellulose in single and combined with Eudragit L100 and Eudragit E100 were used as taste-masking polymers. The obtained microcapsules were characterised by taste-masking ability, in vitro release, SEM, coating thickness, and coating efficiency. Combination of ethyl cellulose and Eudragit E100 (3:1) in coating thickness of 45.13 ± 2.12% w/w prevents AZI release from microcapsules below bitter taste threshold (1.78 ± 1.17 µg/ml). Bioavailability of powders containing AZI microcapsules and pH modulators (50 mg Na3PO4 and 35 mg Mg(OH)2) was not significantly different from the reference product (Zithromax®, Pfizer, New York, NY) in the rabbit model (p > 0.05). These results support the possibility of developing a generic product containing AZI.

Formulation and Evaluation of Microspheres as an effective Colon Targeting Drug Delivery System

The present work comprised of the preparation of coated HPMC capsules of meloxicam microspheres in order to target the drug release in colon resulting in increased absorption and subsequent bioavailability. The meloxicam microspheres were developed in nineteen different batches using HPMC, combination of EC with HPMC, Eudragits (S100, RS100 and E100) in different drug and polymer ratios by solvent evaporation method. The formulation of different batches were examined by various studies i.e. percentage yield, surface morphology (SEM), particle size analysis, entrapment efficiency, drug compatibility with polymers using FTIR and in-vitro drug release determinations. The complex of meloxicam with β-cyclodextrin increased the solubility of the drug accompanying its in-vitro release. The microspheres filled HPMC capsules were coated with eudragit S100 which proved to be an effective method for drug targeting to the colon. A 22 factorial design showed that a very significant increase in release of the drug using polymers i.e. HPMC, E.C with HPMC, Eudragit S100, Eudragit RS100, Eudragit E100 could be obtained by the exclusive manipulation of two variables i.e. surfactant and polymer concentrations. The drug loaded microspheres showed percentage drug entrapment as 35.09-62.50% in A1-A4, 76.29-87.78% in B1-B4, 81.36-92.70% in S1-S4, 65.47-69.4% in RS1-RS4 and 68.91-78.08% in E1-E3. The pH 7.4 phosphate buffer and simulated colonic fluid were used for the in-vitro release tests. The best drug release profiles were seen with formulations A3, B2, RS1, S1 and E2 (containing different ratios of drug: polymer) coated with 15% (w/v) Eudragit S-100 solution.

Polymer coated polymeric microneedles for intravitreal delivery of dexamethasone

The polymer coated polymeric (PCP) microneedles (MNs) is a novel approach for controlled delivery of drugs (without allowing release of the excipients) to the target site. PCP MNs was explored as an approach to deliver the drug intravitreally to minimize the risks associated with conventional intravitreal injections. The core MNs was fabricated with polyvinyl pyrrolidone K30 (PVP K30) and coating was with Eudragit E100. Preformulation studies revealed that the films prepared using Eudragit E 100 exhibited excellent integrity in the physiological medium after prolonged exposure. FTIR studies were performed to investigate the possible interaction between the API and the polymer. The PCP MNs fabricated with different drug loads (dexamethasone sodium phosphate) were subjected to in vitro drug release studies. The drug release from uncoated MNs was instantaneous and complete. On the other hand, a controlled release profile was observed in case of PCP MNs. Likewise, even in the ex vivo porcine eye model, the drug release was gradual into the vitreous humor in case of PCP MNs. The uncoated microneedles released all the drug instantaneously where the PCP MNs retarded the release up to 3 h.

Eudragit Films as Carriers of Lipoic Acid for Transcorneal Permeability

Diabetes mellitus (DM) is a highly prevalent disease affecting almost 10% of the world population; it is characterized by acute and chronic conditions. Diabetic patients have twenty-five times higher risk of going blind and developing cataracts early than the general population. Alpha-lipoic acid (LA) is a highly valuable natural antioxidant for the prevention and treatment of ophthalmic complications, such as diabetic keratopathy and retinopathy. However, its applicability is limited due to its low solubility in water; therefore, suitable systems are required for its formulation. In this work we developed an erodible insert based on Eudragit E100 (E PO) and Lipoic Acid (LA) for the delivery of this compound for the preventive treatment of ocular diseases especially in diabetic patients. Film evaluation was carried out by mechanical and thermal properties, mucoadhesivity, drug release, dynamic light scattering and corneal permeability as the concentration of LA increased. It was shown that upon LA release, it forms nanoparticles in combination with E PO that favor corneal permeation and LA retention in the cornea. These E PO-LA films also resulted non-irritable hence they are promising for their application in the treatment of ocular diseases.

Controlled Release Levetiracetam Loaded Eudragits Microspheres for Oral Drug Delivery: Preparation and Evaluation

This work aims to prepare controlled release microspheres loaded with levetiracetam (LEV) for oral use that will have a targeted release site, thus reducing dose frequency and improving patient compliance. Levetiracetam is a 2nd generation antiepileptic medication with a T/half-life of 7 hours that is administered twice daily, which makes it suitable for formulation that will reduce dosing intake. The microspheres were prepared by solvent evaporation method using Eudragit E100, L100, and S100 polymers as matrix core polymers at diff erent ratios 1:1, 1:2 and 1:3 with levetiracetam. These polymers have diff erent pH sensitivity profi les, which will aid the release of levetiracetam in a controlled manner along the gastrointestinal tract. The prepared microspheres were evaluated for yield percentage, entrapment effi ciency (EE%), morphological characteristics and in-vitro release profi le. The yield percentage and EE% for the formulation at diff erent ratios ranged from 69–99%. The in-vitro release analysis showed favorable targeted release of the drug at specifi c pH ranges matching specifi c sites in the gastrointestinal tract.

Biological properties of chitosan/Eudragit E 100 and chitosan/poly(4-vinylpyridine) coatings electrophoretically deposited on AgNPs-decorated titanium substrate

The objective of the study was the determination of the response, in contact with human osteoblast-like MG-63 cells, of electrophoretically deposited coatings composed of chitosan (CS), Eudragit E 100 (EE100), or poly(4-vinylpyridine) (P4VP) on a silver nanoparticle (AgNPs)-decorated titanium substrate. Before deposition, the substrate was coated with silver by electro-reduction of silver nitrate. The coatings deposition was carried out in suspensions containing 0.1 % (w/w) of one of the biopolymers, EE100 or P4VP, with 0.1 % (w/w) of CS for 10 V and 1 min. Biopolymer coatings were successfully deposited while maintaining high uniformity. The deposited silver did not cause cytotoxicity. The biological study revealed that when compared to CS/P4VP, CS/EE100 coating performed better and showed a decrease in MG-63 cell viability only after three days of testing.

FTIR spectroscopy based identification and compatibility studies of Gamma Oryzanol with various polymers

It is possible to recognise ɣ-oryzanol, also known as Oliver, through the utilisation of an infrared spectroscopy technique. Infrared spectroscopy is a technique that is applied in a variety of fields, including research and industry, to measure a wide range of compounds and to carry out quality control. The numerous peaks that are present in the structure of ɣ-oryzanol were able to be discovered through the use of an IR spectroscopic technique. After that, the values of these peaks were compared to the normative reference standards to ascertain the functional groups that are included in the structure of ɣ-oryzanol. Infrared spectroscopy can, as a result, also be utilised for structural elucidation. During the course of this research, IR spectroscopy was utilised to ascertain whether or not Oliver is compatible with several different polymers. These polymers included HPMC, Sodium carboxy methyl cellulose, Eudragit E-100, Eudragit L-100, Eudragit RLPO and Carbopol 934. By analysing the peaks that appeared at various wavenumbers, it was possible to conclude that ɣ-Oryzanol can be combined well with several different polymers like Eudragit E-100, Eudragit L-100, Eudragit RLPO, HPMC, Sodium carboxy methyl cellulose, and Carbopol 934. Based on the findings of this research, it is abundantly obvious that FTIR spectrometry is capable of immediately determining whether or not a range of polymers contain ɣ-oryzanol. When compared to other chromatographic methods that have been described in the literature, the method that is being proposed makes use of commercial software that is not only straightforward, precise, and quick but also incorporates chemometric styles and the Beer-Lambert law. It is possible to complete sample preparation and spectral capture in a span of around five to ten minutes.

Polymer-Coated Polymeric (PCP) Microneedles for Controlled Dermal Delivery of 5-Fluorouracil.

Polymeric microneedles were prepared with Polyvinyl Pyrrolidone (PVP) K-30 using the mold casting technique. The core microneedles were coated with Eudragit E-100 by dip and spin method. The amount of 5-fluorouracil (FU) loaded in the core microneedles was 604 ± 35.4µg. The coating thickness was 24.12 ± 1.12µm. The objective was to deliver the 5-FU gradually in a controlled release manner at the target site in the sub-stratum corneum layer. This approach is anticipated to improve the safety and efficacy of topical melanoma treatment. The release of the drug was prolonged for up to 3h from the polymer-coated polymeric (PCP) microneedles. The entire amount was found to release within 15min in uncoated MNs. Likewise, the permeation of the drug from the uncoated microneedles was rapid, whereas the PCP microneedles were able to prolong the permeation up to 420min. The PCP microneedles were subjected to stability studies at 25°C ± 2°C/60%RH, and 40°C ± 2°C/75%RH condition for 3months. The formulations were found intact, and the release rate was not significantly different form the fresh formulation. The drug content was found to meet the acceptability criteria as well (98.12 ± 1.8% and 97.8 ± 2.1% at 25 and 40°C respectively after 3months). Overall, this study demonstrated the feasibility of fabrication of PCP microneedles using Eudragit E100 for intraregional controlled delivery of drugs.

PREPARATION AND CHARACTERIZATION OF SONNERATIA ALBA LEAF EXTRACT MICROCAPSULES BY SOLVENT EVAPORATION TECHNIQUE

Objective: Sonneratia alba leaves were used by the community for traditional medicine to cure muscle pain, back pain, antioxidants, rheumatism, malaria, wounds, tuberculosis (TB) and as a spermicide. S. alba leaves extract was easy to damage because of the light exposure, change of pH, weather and a long period of storage time. The problem can be solved by coating the extract with a microencapsulation technique. The purpose of this research was to formulate the microcapsules of S. alba leaves extract with solvent evaporation technique using Ethocel 10 cP and Eudragit E100 as a matrix. Methods: S. alba leaves were extracted using ethanol 96%. This extract was dried by a rotary evaporator. The microencapsulation process of S. alba leaves extract was done by solvent evaporation technique (O/W: oil in water). The formula of S. alba leaves extract microcapsules was designed into six formulas (Eudragit E100: EA1, EA2, EA3 and Ethocel 10 cP: EB1, EB2, EB3). Microcapsules of S. alba leaves extract were characterized for particle size in terms of surface morphology by scanning electron microscope (SEM) and encapsulation efficiency. Antioxidant activity of the formulation have been evaluated by DPPH method. Physical characterization on microparticles was performed by conducting entrapment efficiency and SEM picture. Results: In this research, the microparticles containing S. alba extract has been developed by using ethyl cellulose (Ethocel 10 cP) and eudragit (Eudragit E100) as the polymer matrix. The results showed that a high concentration of polymer (Ethocel 10 cP and Eudragit E100) used in microencapsulation resulted in better S. alba leaves extract microcapsules in terms of physical characteristics. Particle size of microcapsules containing S. alba leaves extract were in the range of 0.701 to 1.163 μm. Encapsulation efficiency (% EE) was categorized as poor because the value were ≤ 80% to which 74.386% (EB3) and 75.248% (EA1). SEM picture of EA1 (Eudragit E100) revealed that the surface of microcapsule were rough and porous. When Ethocel 10 cP was used as a polymer, a smoother surface and less visible pores of microcapsule were obtained. The antioxidant ability of S. alba leaves extract microcapsule showed that IC50 values were 53.26 ppm. Conclusion: It can be concluded that microcapsules of S. alba leaves extract can be prepared by solvent evaporation technique using Eudragit E100 and Ethocel 10 cP as polymer. S. alba leaves has potent antioxidant activity either as an extract or after being formulated into microcapsules.

EVALUATING THE IMPACT OF SOLID MICRONEEDLES ON THE TRANSDERMAL DRUG DELIVERY SYSTEM FOR Ɣ-ORYZANOL

Objective: This study's goals were to develop a minimally invasive array of biocompatible polymeric solid microneedles and formulate a transdermal patch of drug Ɣ-Oryzanol as per poke and patch technology. Methods: Scanning electron microscopy was used to analyse the morphology of the solid microneedle arrays, which were created using a stereolithography (SLA) printer with high-resolution capabilities (25 and 140 microns for the z and x axes, respectively). Transdermal Patches of Ɣ-Oryzanol were formulated and evaluated for various characterization parameters. Further, the produced microneedle-transdermal drug delivery system of Ɣ-Oryzanol was examined for microneedle insertion skin and permeation of the drug across the porcine skin. Results: Solid microneedle arrays were manufactured using biocompatible Class I Dental SG resin having dimensions of 600 µm height and 300 µm width with tip diameters of 30 µm and 1.85 mm interspacing (Distance from tip to tip) and they were strong enough to penetrate porcine skin to a depth of 381.356 µm crossing the stratum corneum layer without causing any structural changes. Transdermal patches containing Ɣ-Oryzanol were formulated using different ratios of HPMC: Eudragit E-100. Good, consistent, and transparent films were formulated when the thickness of the film ranges between 0.516±0.25-0.628±0.21 mm, average weights ranged from 168.23±2.61to171.22±1.25(10/cm2), folding endurance ranged in between 10 folds to 12 folds for all the formulations with tensile strength lie between the 0.365 kg/mm2 to 0.465 kg/mm2. All the formulations showed good drug content between 99.3±0.06%-90.4±1.64% with 100% flat surfaces. Moisture content was found in the range of 2.012±0.013 to 4.213±0.031. Drug permeation studies reveal that compound Ɣ-Oryzanol transdermal patches didn’t show significant permeation across porcine skin (4.802.25 g/cm2) without piercing with microneedles while after poking skin using microneedles (74.502.35 g/cm2) drug showed good penetration properties. It was found that the amount of drug delivered increased to 44.251.57 g/cm2 at 2 min, which was 14.502.35 g/cm2 at 1 min to 4 min 74.502.35 g/cm2. Conclusion: Successful preparation of the Microneedle-Transdermal drug delivery system of Ɣ-Oryzanol and their evaluation indicated that the quality and consistency of the formulated preparation were excellent. With advantages in terms of lowered dose frequency, better patient compliance, and bioavailability, this may find use in the therapeutic field.

Microfluidic Particle Engineering of Hydrophobic Drug with Eudragit E100─Bridging the Amorphous and Crystalline Gap.

Co-processing active pharmaceutical ingredients (APIs) with excipients is a promising particle engineering technique to improve the API physical properties, which can lead to more robust downstream drug product manufacturing and improved drug product attributes. Excipients provide control over critical API attributes like particle size and solid-state outcomes. Eudragit E100 is a widely used polymeric excipient to modulate drug release. Being cationic, it is primarily employed as a precipitation inhibitor to stabilize amorphous solid dispersions. In this work, we demonstrate how co-processing of E100 with naproxen (NPX) (a model hydrophobic API) into monodisperse emulsions via droplet microfluidics followed by solidification via solvent evaporation allows the facile fabrication of compact, monodisperse, and spherical particles with an expanded range of solid-state outcomes spanning from amorphous to crystalline forms. Low E100 concentrations (≤26% w/w) yield crystalline microparticles with a stable NPX polymorph distributed uniformly across the matrix at a high drug loading (∼89% w/w). Structurally, E100 incorporation reduces the size of primary particles comprising the co-processed microparticles in comparison to neat API microparticles made using the same technique and the as-received API powder. This reduction in primary particle size translates into an increased internal porosity of the co-processed microparticles, with specific surface area and pore volume ∼9 times higher than the neat API microparticles. These E100-enabled structural modifications result in faster drug release in acidic media compared to neat API microparticles. Additionally, E100-NPX microparticles have a significantly improved flowability compared to neat API microparticles and as-received API powder. Overall, this study demonstrates a facile microfluidics-based co-processing method that broadly expands the range of solid-state outcomes obtainable with E100 as an excipient, with multiscale control over the key attributes and performance of hydrophobic API-laden microparticles.

Cationic polymer contributes to broaden the spectrum of vancomycin activity achieving eradication of Pseudomonas aeruginosa.

Vancomycin (VAN) is unable to penetrate the outer membrane of Gram-negative bacteria and reach the target site. One approach to overcome this limitation is to associate it with compounds with permeabilizing or antimicrobial properties. EudragitE100® (Eu) is a cationic polymer insufficiently characterized for its potential antimicrobial action. Eu-VAN combinations were characterized, the antimicrobial efficacy against Pseudomonas aeruginosa was evaluated and previous studies on the effects of Eu on bacterial envelopes were extended. Time-kill assays showed eradication of P. aeruginosa within 3-6h exposure to Eu-VAN, whilst VAN was ineffective. Eu showed regrowth in 24h and delayed colony pigmentation. Although permeabilization of bacterial envelopes or morphological alterations observed by TEM and flow cytometry after exposure to Eu were insufficient to cause bacterial death, they allowed access of VAN to the target site, since Eu-VAN/Van-FL-treated cultures showed fluorescent staining in all bacterial cells, indicating Van-FL internalization. Consequently, Eu potentiated the activity of an otherwise inactive antibiotic against P. aeruginosa. Moreover, Eu-VAN combinations exhibited improved physicochemical properties and could be used in the development of therapeutic alternatives in the treatment of bacterial keratitis.

Assessment of Once Daily Controlled-release Ibuprofen Matrix Tablets Prepared using Eudragit ®E100/Carbopol® 971P NF Polymers and their Salt Combinations.

Hydrophilic polymers that swell or dissolve in aqueous media can have the potential to prepare controlled/sustained dosage forms for weakly acidic and poorly soluble drugs. The main objective of this study is to utilize Eudragit®E100 (EE) and Carbopol®971P NF (Cp) polymers and their salt forms for the preparation of a once-daily controlled-release matrix tablet for model drug, Ibuprofen (IB). Combinations of the polymers in their base forms (EE)/(Cp) or in their salt forms (EEHCl/ CpNa) were compressed with (IB) into single layer matrix tablets, or otherwise into bilayer tablets. Dissolution profiles were constructed using three different consecutive stages (pH 1.2, 4.8 and 6.8). It was found that the incorporation of (EEHCl) modified the release rates of (IB) from (Cp) based matrix tablets. However, a major enhancement of (IB) release rates occurred when the polymers were combined in their salt forms in a 1:1 ratio by weight. In addition, a bilayer tablet was prepared wherein a relatively rapidly disintegrating layer composed of polymers salts (EEHCl and CpNa), and a second layer containing only (Cp) polymer in its base form in a 1:2 weight ratio possessed excellent release properties and mechanical strength. It was concluded that the prepared bilayer tablet could be promising for controlling the release rates of (IB) in an extended manner to allow once-daily administration with an improved pH-independent release behavior.

A supersaturating drug delivery system to enhance the oral bioavailability of nilotinib

As a weak base, the solubility of nilotinib (NH) decreases with increasing pH resulting in low bioavailability via oral administration. In our study, NH was selected as a model drug to explore a supersaturating drug delivery system (SDDS) to improve the absorption and bioavailability of BCS IV drugs. Certain excipients were used to prevent or delay the precipitation of NH after pH increment. Hence, the solid dispersions of NH were synthesized in the presence of either Eudragit E100 (ESD) or Soluplus (SSD), respectively. Both ESD and SSD are proven to rapidly dissolve in the acidic dissolution medium, forming supersaturated NH solutions after the pH increment to 6.8, while the supersaturated solution of NH was kept stable for a sufficient time period. NH was found to exist in the microcrystalline form in the ESD and amorphous form in the SSD. The relative bioavailability of ESD and SSD in rats was 222% and 219%, respectively, compared with NH suspension, suggesting that the two formulations developed in our study significantly improved the oral absorption of NH. Overall, SDDS represents a promising strategy to improve the oral bioavailability of NH and such platform technology may be explored to other BCS II or IV drugs with poor solubility.