Eudragit RLPO Research Articles

Nanonization and Deformable Behavior of Fattigated Peptide Drug in Mucoadhesive Buccal Films.

This study was tasked with the design of mucoadhesive buccal films (MBFs) containing a peptide drug, leuprolide (LEU), or its diverse nanoparticles (NPs), for enhanced membrane permeability via self-assembled nanonization and deformable behavior. An LEU-oleic acid conjugate (LOC) and its self-assembled NPs (LON) were developed. Additionally, a deformable variant of LON (d-LON) was originally developed by incorporating l-α-phosphatidylcholine into LON as an edge activator. The physicochemical properties of LON and d-LON, encompassing particle size, zeta potential, and deformability index (DI), were evaluated. MBFs containing LEU, LOC, and NPs (LON, d-LON) were prepared using the solvent casting method by varying the ratio of Eudragit RLPO and hydroxypropyl methylcellulose, with propylene glycol used as a plasticizer. The optimization of MBF formulations was based on their physicochemical properties, including in vitro residence time, dissolution, and permeability. The dissolution results demonstrated that the conjugation of oleic acid to LEU exhibited a more sustained LEU release pattern by cleaving the ester bond of the conjugate, as compared to the native LEU, with reduced variability. Moreover, the LOC and its self-assembled NPs (LON, d-LON), equivalent to 1 mg LEU doses in MBF, exhibited an amorphous state and demonstrated better permeability through the nanonization process than LEU alone, regardless of membrane types. The incorporation of lauroyl-L-carnitine into the films as a permeation enhancer synergistically augmented drug permeability. Most importantly, the d-LON-loaded buccal films showed the highest permeability, due to the deformability of NPs. Overall, MBF-containing peptide NPs and permeation enhancers have the potential to replace parenteral LEU administration by improving LEU druggability and patient compliance.

Agarose as a tunable platform for oral drug delivery: Controlled release of a highly soluble drug, theophylline, within a sequentially-changing-pH medium

The purpose of this study was to expand the use of freeze-dried agarose-based systems for the oral controlled release of highly water-soluble drugs. Three additives (Eudragit S-100 and RL-PO and Labrafac) were included within these systems together with Theophylline. The release of this drug from the rehydrated systems was evaluated in deionized water and in a sequentially-changing-pH medium that simulated the conditions under oral administration. Considering the results obtained in the preliminary release test in water, only the Eudragit-containing compositions were further characterized. The theophylline release in a sequentially-changing-pH medium showed two different patterns that mainly depend on the additive nature: those systems containing Eudragit S-100 showed a similar behaviour to that observed in the absence of additives while the presence of Eudragit RL-PO yields a progressive and pH-independent release. Agarose-based systems were capable of accommodating additives that allows tailoring a controlled release of theophylline, a highly soluble drug.

Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfortandefficacy.

Curcumin, known for its anti-inflammatory properties, was selected for the developing consumer friendly film forming spray that offers precise delivery of curcumin and and improves patient adherence. An optimized film-forming solution was prepared by dissolving curcumin (1%), Eudragit RLPO (5%), propylene glycol (1%), and camphor (0.5%) in ethanol: acetone (20:80) as the solvent. The solution was filled in a spray container which contained 70% solutions and 30% petroleum gas. In-vitro characterization was performed. Potential anti-inflammatory phytoconstituents were extracted from the PubChem database and prepared as ligands, along with receptor molecules (nsp10-nsp16), for molecular docking using Autodock Vina. The docking study showed the lowest binding energy of -8.2 kcal/mol indicates better binding affinities. The optimized formulation consisted of ethanol:acetone (20:80) as the solvent, Eudragit RLPO (5%) as the polymer, propylene glycol (1%) as the plasticizer, and camphor oil (0.5%) as the penetration enhancer. The optimized formulation exhibited pH of 5.8 ± 0.01, low viscosity, low film formation time (19.54 ± 0.78 sec), high drug content (8.243 ± 0.43 mg/mL), and extended ex vivo drug permeation (85.08 ± 0.09%) for nine hours. Consequently, the formulation was incorporated into a container using 30% liquefied petroleum gas, delivering 0.293 ± 0.08 mL per actuation, containing 1.53 ± 0.07 mg of the drug. The film-forming spray exhibited higher cumulative drug permeation (83.94 ± 0.34%) than the marketed cream formulation and pure drug solution after 9 h, with an enhancement ratio of 14. Notably, the film-forming spray exhibited no skin irritation and remained stable for over three months. The developed curcumin film-forming system is promising as a carrier for wound management because of its convenient administration and transport attributes. Further in vivo studies are required to validate its efficacy in wound management.

Formulation and Evaluation of Ocusert Embeded with Ciprofloxacin Loaded Nanoparticles

Formulation and Evaluation of Ocusert Embeded with Ciprofloxacin Loaded Nanoparticles

Oxybenzone-loaded Polymeric Nanocapsule Gel: Strategy to Reduce Skin Penetration and Drug-induced Irritation

Aim: This work aimed to determine whether the oxybenzone-loaded nanocapsule gel (NC gel) can reduce the degree of skin penetration and, thereby, the skin irritation caused by the drug. Background: Sunscreens must be retained on the uppermost skin surface, forming a protective film throughout the entire UV exposure period. Skin penetration and/or light-induced decomposition of sunscreens is undesirable as this would decrease the expected UV protection. The changes in colour and appearance of the sunscreen, as well as the possible increase in the phototoxicity and allergenic potential of sunscreen breakdown products, are also of concern. : Furthermore, exposure to UVB radiation leads to impairment in the stratum corneum and hence enhances the skin's penetration of sunscreen actives, leading to systemic absorption. Currently, available sunscreen agents are low-molecular-weight lipophilic molecules, which make them capable of penetrating the skin and being systemically absorbed. : Oxybenzone is an organic compound widely used in commercial sunscreen preparations. The low molecular weight and lipophilic nature of oxybenzone facilitate penetration through the stratum corneum, leading to irritation and allergic reactions. : Polymeric nanocapsules (NCs) have been developed to ensure a controlled release of pharmaceutical and cosmetic agents and/or exert a preventive effect against the harmful side effects induced by direct contact of tissues with high amounts of the drug. Hence, we hypothesised that encapsulating the oxybenzone polymeric nanocapsule system would reduce the irritation and its allergic potential upon topical application. Objective: The current study aimed to develop a polymeric nanocapsule-based gel of oxybenzone and investigate its skin deposition by ex vivo permeation studies. Methods: The polymeric nanocapsules were prepared by the solvent displacement method using a combination of Eudragit RSPO and Eudragit RLPO polymers. Further nanocapsules were incorpo-rated into the xanthan gum gel base. It was evaluated for particle size, PDI, zeta potential, drug con-tent, in vitro release, ex vivo permeation, sunscreen efficacy and skin irritation potential by the HET CAM test. Results: Particle size, PDI, zeta potential, percent encapsulation, and loading of drug-loaded nanocap-sule suspension were found to be 237.1 nm, 0.189 + 58.4 mV, 852 + 0.5%, and 19.45 + 0.94%, re-spectively. DSC results indicate the suitability of selected excipients. In vitro release studies indicated 68.99% oxybenzone release from NC suspension, while NC gel showed 58.87% at the end of 24 hrs. Ex vivo permeation results showed significantly higher drug permeation from plain oxybenzone gel than NC gel. Permeation flux and reduction ratio suggest a three-fold reduction in skin permeation by NC gel. The gel offered medium-level sun protection with an SPF value of 22.12. According to the HET CAM study, there was no evidence of skin irritation caused by NC gel. Conclusion: It is concluded that the encapsulation of oxybenzone prevents direct interaction with the skin, reducing the chances of skin irritation and penetration. Results suggest that nanocapsules in gel bases can provide a promising formula for safer topical delivery of sunscreen.

In-situ formation of nanoparticles from drug-loaded 3D polymeric matrices

The in-situ formation of nanoparticles from polymer-based solid medicines, although previously described, has been overlooked despite its potential to interfere with oral drug bioavailability. Such polymeric pharmaceuticals are becoming increasingly common on the market and can become even more popular due to the dizzying advance of 3D printing medicines. Hence, this work aimed to study this phenomenon during the dissolution of 3D printed tablets produced with three different polymers, hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyvinyl alcohol (PVA), and Eudragit RL PO® (EUD RL) combined with plasticizers and the model drug naringenin (NAR). The components' interaction, dissolution behavior, and characteristics of the formed particles were investigated employing thermal, spectroscopic, mechanical, and chromatographic assays. All the systems generated stable spherical-shaped particles throughout 24 h, encapsulating over 25% of NAR. Results suggest encapsulation efficiencies variations may depend on interactions between polymer-drug, drug-plasticizer, and polymer-plasticizer, which formed stable nanoparticles even in the drug absence, as observed with the HPMCAS and EUD RL formulations. Additionally, components solubility in the medium and previous formulation treatments are also a decisive factor for nanoparticle formation. In particular, the treatment provided by hot-melt extrusion and FDM 3D printing affected the dissolution efficiency enhancing the interaction between the components, reverberating on particle size and particle formation kinetics mainly for HPMCAS and EUD RL. In conclusion, the 3D printing process influences the in-situ formation of nanoparticles, which can directly affect oral drug bioavailability and needs to be monitored.

Development and Evaluation of Luliconazole Nail Lacquer Containing Potential Permeation Enhancers for an Enhanced Transungual Drug Delivery

Background: Topical therapy for nail infection has a serious drawback of drug permea-tion via keratinized human nail plate. Onychomycosis, or tinea unguium, is a human nail fungal infection affecting nearly 19% of the world’s population. Aim: Purposely, we aimed to develop and evaluate nail lacquer formulations incorporated with lu-liconazole utilizing different permeation enhancers for targeted transungual drug delivery. Nail clippings were treated with luliconazole solution (5% w/v) with or without permeation enhancers and screened by determining the hydration enhancement factor and retention of the drug in the nail clippings. Different batches of nail lacquer formulations were prepared to employ Eudragit, poly-ethylene glycol 400, Tween 80, and permeation enhancer with the highest hydration enhancement factor value. Methods: Successively, the formulations were evaluated for studies like compatibility, application, gloss, blush, smoothness of flow, adhesion, non-volatile content, etc. Based on the results of physi-cal characterization and in vitro release study, formulations based on Eudragit RLPO and RSPO containing N-acetylcysteine and urea and the Eudragit RL100 containing urea as penetration en-hancer were found to be potentially useful. Furthermore, a comparative ex vivo evaluation of the formulations for permeation across the nail clippings revealed that the luliconazole-loaded Eudragit RLPO formulations containing N-acetylcysteine and urea provided the highest flux (5.12 μg/cm2/min) and shortest lag time (17.4 min). Results: Morphological analysis showed an increase in the number of pores on the nail surface, leading to the enhancement of drug diffusion across the nail matrix and nail bed. Conclusion: Furthermore, the luliconazole nail lacquer formulation exhibited higher antifungal ac-tivity, viscosity, and stability properties. Hence, the results suggest that the developed luliconazole nail lacquer formulation is an efficient topical transungual drug delivery system.

Exploration of polymethacrylate and Hypromellose for the development of a non-sulfhydryl ACE inhibitor mucoadhesive system using Box-Behnken design: in-vitro and ex-vivo evaluation

Purpose To counteract early morning pathology like hypertension a time-dependent release of the drug is required. This study is focused to formulate a pulsatile and mucoadhesive drug delivery system of an ACE inhibitor Perindopril Erbumine. Method Two matrix tablets were punched with Eudragit RSPO, Eudragit RLPO, and HPMC K15M using a 3-3-3 Box-Behnken Design of Response Surface Methodology. Based on the design-optimized formulation P1T3 and P2T8 were coated for a lag time with compression coating of HPMC K4M and a blend of 1:1 ratio of ethylcellulose and carbopol polymer and further encapsulated in a Eudracap™ capsule to provide gastric resistance. Result The in-vitro release data confirmed an initial pause phase of 4.5 h then release of the drug for 5.2 ± 0.3 h to cope with the early morning rush in blood pressure. After that, a gap of 6 h and then sustained release of the drug for 10.5 ± 0.5 h. From the ex-vivo study, mucoadhesive strength was obtained as 55.13 ± 0.03 gm and 56.39 ± 0.02 gm for P1T3 and P2T8 respectively. The lag time for coated tablet P1T3 came to 2.15 ± 0.15 h and for P2T8 11.9 ± 0.10 h proving the coating efficiency of polymers. Conclusion The current study strongly suggests that perindopril Erbumine in association with Eudragit and Hypromellose polymer can open a path for the time-regulated release of the drug for hypertension chronotherapy with less risk of dose dumping.

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.

Cross-linked Alginate Beads of Montelukast Sodium Coated with Eudragit for Chronotherapy: Statistical Optimization, In vitro and In vivo Evaluation.

Chronotherapy is the administration of medication according to the biological rhythm to maximize pharmacological effects and minimize side effects. The objective of the current investigation is to prepare delayed-release beads (DRBs) containing montelukast sodium (MKS) for chronotherapy of asthma. Delayed-release beads of alginate were prepared using a simple method, i.e., ionotropic gelation. The effect of cross-linking agents (zinc or calcium ions) and the concentration of chitosan on the properties of the beads were investigated. The prepared beads were coated by a polymer having pHindependent solubility, i.e., Eudragit RSPO and Eudragit RLPO in different ratios to achieve the desired lag time of 4-5 h. Beads were evaluated for surface morphology, practical yield, encapsulation efficiency, XRD, and in vitro release study. The pharmacokinetic study was carried out on New Zealand white male rabbits. No major differences in the drug release profile were observed between Ca++ and Zn++ crosslinked beads. However, a slight slow release was seen in the case of chitosan-reinforced beads. MKS released from cross-linked alginate beads was slightly altered with sodium alginate concentration, crosslinking time, and talc. At a higher alginate concentration, slow drug release was observed, whereas the addition of talc to alginate increased the release rate. The in vitro release study showed that the optimal formulation of DRBs has a lag time of 4.5 h, and the release at 6 h was found to be 74.9%. In vivo pharmacokinetic study of the beads showed Tmax at 7 h with an initial lag time of 4 h. When dosed at sleep time, the prepared cross-linked beads may deliver montelukast sodium required to relieve early morning symptoms in asthmatic patients.

Formulation, Development and Characterization of Transdermal Patches of Glipizide

Transdermal patches are innovative drug delivery systems and can be used for achieving efficient systemic effect by passing hepatic first pass metabolism and increasing the fraction absorbed. Like other drugs among the second-generation sulfonylureas, glipizide (GLP) acts by stimulating insulin secretion from pancreatic beta-cells as well as modifying the responsiveness of insulin-sensitive tissues. GLP belongs to biopharmaceutical classification system (BCS) class II and has a low solubility and high permeability. The aim of the current research was to formulate GLP transdermal patches utilizing various polymers combinations. HPMC, ethyl cellulose, eudragit RLPO, eudragit RSPO and permeation enhancer were mixed in different ratios, in presence of polyethylene glycol 400 as plasticizer by the solvent casting evaporation technique. The physicochemical parameters such as flexibility, thickness, smoothness, weight variation, moisture content, hardness, folding endurance and tensile strength were evaluated for the prepared patches. The formulation exhibited flexibility, uniform thickness and weight, smoothness, good drug content (98.65±0.26 to 99.45±0.65%) and little moisture content. The in vitro diffusion studies were carried out using modified Franz diffusion cell using egg membrane as the diffusion membrane and the formulation followed the zero order diffusion mechanism. The formulation containing HPMC: Eudragit as polymers showed faster release rate compared to ethyl cellulose: eudragit. The stability studies indicated that all the patches maintained good physicochemical properties and drug content after storing the patches in different storage conditions. Compatibility studies indicated that there was no interaction between the drug and polymers. The results revealed that, GLP transdermal patch could be considered as promising drug delivery system for diabetic patients. Keywords: Transdermal patches, Glipizide, Sulfonylureas, Physicochemical parameters, In vivo diffusion study

FORMULATION OF MESALAMINE-LOADED RECTAL MUCOADHESIVE PELLETS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE USING 32FULL FACTORIAL DESIGN

Objective: The objective of the present work was to optimize a rectal suppository containing mucoadhesive pellets of Mesalamine to achieve local yet sustained release of Mesalamine for once-a-day administration for the therapy of Inflammatory Bowel Disease. Methods: Thus, the present work involves forming mucoadhesive pellets of mesalamine by extrusion spheronization, which were then loaded into a suppository to be administered rectally. The pellets were evaluated for mucoadhesion strength, swelling potential, morphology, particle size, drug release, drug loading and retention time. Results: The optimized batch of pellets using Eudragit RLPO as the release retardant, carrageenan as a mucoadhesive polymer and other excipients had a mucoadhesion strength of 0.143 N, a swelling index of 50.50 %, and 44 % and 75 % drug was released from them at the end of 6 and 15 h respectively. The pellets-loaded cocoa butter suppositories had a melting range of 35–37 °C, disintegrated within 8–9 min and had a hardness of 4–5 kg/cm3. A comparison of the in vitro drug release profile from the mucoadhesive pellets and the mucoadhesive pellets-loaded suppositories showed a closeness in the % cumulative drug release indicating that cocoa butter did not interfere in the release of the drug from the pellets. Conclusion: Mucoadhesive Pellets were successfully developed by extrusion spheronizer technique and incorporated into suppositories. In vitro study revealed a release profile that warranted a once-a-day regimen leading to a reduction in the requirement of the drug and hence the side effects.

Compression-coated pulsatile chronomodulated therapeutic system: QbD assisted optimization

Pulsatile drug delivery systems have drawn attention in contemporary research for designing chronotherapeutic systems. The current work aims to design pulsatile ketorolac tromethamine tablets using compression coating for delayed delivery with a lag time suitable for the treatment of morning stiffness in arthritis. Rapidly disintegrating core tablets of ketorolac tromethamine were formulated using super-disintegrants, and the optimized formulation was compression using PEO WSR coagulant and Eudragit RLPO for delaying the release. The central composite design and response surface methodology were employed to optimize the formulation and process parameters namely PEO WSR Coagulant (X1), Eudragit RLPO (X2), and Hardness (X3). The dependent variables optimized were lag time and time required for 95% drug release. Analysis using response surface graphs and mathematical modeling of the results allowed identifying and quantifying the formulation variables active on the selected responses. A polynomial equation fitted to the data was used to predict the composition with optimum responses. Compression-coated pulsatile tablets’ optimized composition exhibited a lag time of 9 h and released 95% of the ketorolac tromethamine in 17.42 h. Validation of the mathematical model assured the reliability of QBD in formulation design. In vivo X-ray imaging and pharmacokinetic studies established a strong relationship between the coated polymers maintaining the desired lag time for delayed delivery of the active to coincide with the chronobiology for enhanced bioavailability at the right time when needed.

Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Formulation and evaluation of transdermal patches of nitrendipine eudragit RLPO and RSPO using rate controlling polymers

Formulation and evaluation of transdermal patches of nitrendipine eudragit RLPO and RSPO using rate controlling polymers

Development and Evaluation of Controlled Release Formulations of Esomeprazole

The present work was aimed to development of controlled release formulations of Esomeprazole to improve bioavailability. Esomeprazole is the proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity. Construction of calibration curve of Esomeprazole and to investigate the drug and polymer interaction studies by FTIR and DSC. To prepare the different controlled release formulations of Esomeprazole tablets with different polymers like Polymethacrylates such as Eudragit-S100, Eudragit-L100, Eudragit-RSPO, Eudragit-RS100, Eudragit-RL100 and Eudragit RLPO by Direct Compression method. Evaluation of Esomeprazole pre compression parameters such as Bulk density, Tapped density, Hausner’s ratio, Carr’s index, Angle of repose. Evaluation of post-compression parameters of Esomeprazole controlled release tablets such as Weight variation, Hardness, Friability test, Thickness, Drug Content and In-vitro dissolution studies. Evaluation of in-vitro dissolution uniqueness of all the formulations of Esomeprazole by using USP dissolution apparatus type-II (paddle). To study the mechanism of drug dissolution by applying kinetic parameters. To perform the stability studies of optimized formulations of Esomeprazole as per ICH guidelines.

Cationic Polymeric Nanoparticles for Improved Ocular Delivery and Antimycotic Activity of Terconazole

Terconazole (TCZ) is a broad-spectrum antifungal triazole that is particularly active against Candida species, but its poor water solubility hinders its ocular absorption and restricts its application. This study aims to fabricate TCZ-loaded cationic polymeric nanoparticles to enhance the ocular delivery and antimycotic activity of terconazole. TCZ-loaded nanoparticles were developed by nanoprecipitation method employing Eudragit RLPO®. They were characterized by entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), morphology, Fourier transform infrared spectroscopy (FT-IR), and X-ray powder diffraction (XRPD). In-vitro antimycotic activity was evaluated by measuring zone of inhibition (ZI), minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The developed nanoparticles were spherical with moderate to high EE% (44.03–71.14%), a nanometric PS (49.41–78.72 nm), and a positively charged ZP (≥ +21.47). In-vitro release studies revealed sustained release of drug up to 24 h. FT-IR of TCZ-loaded nanoparticles revealed distinctive peaks for Eudragit RLPO® and Poloxamer-188, with disappearance of the TCZ characteristic peaks. XRPD revealed the amorphous state of TCZ within the polymer matrix. Mucoadhesive studies proved the mucoadhesive property of the developed TCZ nanoparticles. In-vitro antimycotic studies, assessed by ZI, MIC and MFC, revealed enhanced antimycotic activity of TCZ-loaded nanoparticles against Candida albicans, relative to plain TCZ. No irritation or abnormal changes to the rabbits’ eyes for plain and medicated polymeric nanoparticles were found by the in-vivo Draize test. These findings reveal that the cationic polymeric nanoparticles can be regarded as a potential drug delivery system for enhancing the ocular antimycotic activity of TCZ.

Optimization of amorphous solid dispersion techniques to enhance solubility of febuxostat.

Febuxostat is a selective inhibitor of xanthine oxidase and belongs to BCS class II drugs having low solubility and high permeability. Solubility is the most important parameter which directly affects dissolution, absorption and bioavailability of the drugs. There are different techniques by which we can improve solubility and dissolution rate of poorly soluble drug. Amorphous solid dispersion is one of the methods which can improve solubility as well as powder characteristics. The aim of the present study was to formulate and optimize various methods of formulating solid dispersion by using various drug-to-polymer ratios and identifying the batch which gives higher solubility as well as amorphous powder of the drug febuxostat. Different techniques like hot melt method, solvent evaporation method and spray drying techniques were selected for optimization. Attempts were made to improve solubility of febuxostat by employing Kolliphor P 188, Kolliphor P 237, Eudragit RLPO in different drug-to-polymer ratios (1:1, 1:1.5, 1:2) as carrier. The prepared solid dispersion was characterized for the saturation solubility, percentage yield, using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powdered X-ray diffraction studies (PXRD), and residual solvent determination. Solid state characterization indicated that febuxostat was present in the amorphous form after mixing with polymeric carrier. In contrast to the pure form of drug, solid dispersion of the drug showed better solubility and amorphous characteristics which can be attributed to decreased crystallinity due to hydrotrophy. Thus, amorphous solid dispersion approach can be used successfully to enhance solubility, dissolution rate and bioavailability of febuxostat.

Oleic acid–reinforced PEGylated polymethacrylate transdermal film with enhanced antidyslipidemic activity and bioavailability of atorvastatin: A mechanistic ex-vivo/in-vivo analysis

To enhance the poor bioavailability and extensive liver metabolism of atorvastatin calcium (ATC), we have developed an oleic acid–reinforced PEGylated polymethacrylate (OLA–PEG–E-RLPO) transdermal film as a convenient and alternative delivery system. The effect of varying levels of Eudragit RLPO, PEG 400, and oleic acid on the target product profile was optimized through Quality by Design (QbD) approach. The ATC–loaded OLA–PEG–E-RLPO transdermal films were evaluated in ex-vivo experiments using full thickness skin, utilizing Franz cell studies, and undergone in-vivo pharmacokinetics/pharmacodynamics (PK/PD) assessment, using poloxamer-induced dyslipidemic Sprague-Dawley rats. At 2 and 12 h, the optimized ATC films with a thickness of 0.79 mm showed permeation of 37.34% and 97.23% into the receptor compartment, respectively. Steady-state flux was 0.172 mg/cm2h, with 7.01 × 10−4 cm/h permeability coefficient, and 0.713 × 10−3 cm2/h diffusion coefficient. In-vivo PK results indicated that the absorption profiles (AUC0-∞) of the optimized film in pre-treated group of animals were 8.6-fold and 2.8-fold greater than controls pre-treated with non-PEGylated non-oleic acid film and orally administered ATC, respectively. PD assessment of the lipid panel indicated that the lipid profile of the optimized film pre-treated group reached normal levels after 12 h, along with the significant enhancement over the non–PEGylated non-oleic acid film and the oral marketed tablet groups. The histopathological findings revealed near-normal hepatocyte structure for the optimized film pre-treated animal group. Our results further indicate that transdermal delivery films based on an optimized ATC–loaded OLA–PEG–E-RLPO were successfully developed and their assessment in both ex-vivo and in-vivo suggests enhanced permeability and improvement in bioavailability and antidyslipidemic activity of ATC. This approach can provide several advantages, especially during chronic administration of ATC, including improvement in patient compliance, therapeutic benefits, bioavailability, and feasibility for commercialization and as a platform for other drug classes.

FORMULATION AND EVALUATION OF SUSTAINED-RELEASE PELLETS OF LORNOXICAM

Objective: The aim of the study was to develop sustained release pellets of lornoxicam using Eudragit RLPO and Eudragit RSPO to reduce the dosing frequency.
 Methods: The sustained release pellets of lornoxicam were prepared by extrusion–spheronization technique using Eudragit RLPO and Eudragit RSPO as release retardant polymers and microcrystalline cellulose as spheronizing agent. A 32 Full factorial design was applied to investigate the combined effect of the two independent variables i.e. concentration of Eudragit RLPO (X1) and concentration of Eudragit RSPO (X2) on the dependent variables, In vitro drug release at 1h (Y1), In vitro drug release at 4 h (Y2) and In vitro drug release at 12 h. (Y3).
 Results: The optimized formulation (F0) show in vitro drug release 11.24±1.21 %, 43.69±1.28 %, 82.69±1.74 % and 100.24±1.56 % at 1 h, 4 h, 12 h and 24 h respectively. Drug excipients compatibility study by FTIR showed no interaction between drug and excipients. Eudragit RLPO and Eudragit RSPO had a significant effect on in vitro drug release.
 Conclusion: From all parameters and experimental design evaluation, it was concluded that the drug release rate decreased with an increase the concentration of Eudragit RLPO and Eudragit RSPO. SEM Photomicrograph of pellets revealed that the surface was rough and the pellets were spherical shaped in nature. The in vitro release kinetics revealed higuchi model is followed and drug release is by anamolous diffusion.