Development, characterization, and in vitro evaluation of adhesive fibrous mat for mucosal propranolol delivery

This research focuses on the synthesis and adhesive properties of mucoadhesive mats, prepared with poly(vinylic alcohol) as a base polymer for the oromucosal release of propranolol (PRO) by the electrospinning technique. The nanofibers mats were evaluated by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry; in vitro drug entrapment efficiency, degradation time, and adhesion studies were performed. SEM images of the electrospun mats show the correct formation of fibers with a variable diameter and porosity. Thermal studies indicate excellent thermal stability of the scaffolds, The fibrous mats loaded with 10% of the drug exhibit the best thermal stability with decomposition after 450°C. In vitro studies indicate a drug content of 88% loaded in the mats. In the cytotoxicity test, loaded mat presents cell proliferations of 97% and 88% for drug concentrations of 10% an 15%, respectively. To conclude, the formed electrospun adhesive mats exhibited excellent thermal stability, adhesive properties, and drug entrapment efficiency, promising features for a successful drug topical release system on mucosal tissue in the oral cavity.

Formulation, optimization, and characterization of amlodipine besylate loaded polymeric nanoparticles

The objectives of this work were to formulate and optimize amlodipine besylate loaded polymeric nanoparticles by using factorial design. The emulsion solvent evaporation method was employed successfully to produce the drug loaded polymeric nanoparticles and the optimization was done by the help of the 24 factorial design. The effect of the main preparation variables on the dependent variables such as nanoparticle size and % drug entrapment efficiency was studied for the optimization of the nanoparticles. The characterization of these nanoparticles was done by the different parameters such as interaction between the excipients, size, morphology, zeta potential, % drug entrapment efficiency, % process yield, and in-vitro drug release behavior. FTIR, DLS, TEM, AFM, zeta potential studies, and dialysis bag method were performed for this purpose. The in vitro drug release data were analyzed by different kinetic models to know the release mechanism. The optimized nanoparticles were spherical in shape and showed particle size 91.5 ± 4.3 nm, PDI 0.368 ± 0.014, zeta potential −17.5 mV, % drug entrapment efficiency 74.06 ± 2.1%, and % process yield 78.51 ± 1.8%. The release kinetics studies revealed that drug release from the nanoparticles follow the Korsmeyer–Peppas model.

Formulation and Characterization of Modified Release Microspheres of Lornoxicam Using Okra Gum as Natural Polymer and Ethyl Cellulose as Synthetic Polymer

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated. Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release. Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model. In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n < 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model. Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

Application of Design of Expert software for evaluating the influence of formulation variables on the encapsulation efficacy, drug content and particle size of PEO-PPO-PEO/Poly(DL-lactide-co-caprolactone) nanoparticles as carriers for SN-38

Background and aims. Hydrophobic substances are mainly encapsulated into polymer nanocarriers in order to improve their solubility, enable their administration, at the same time to empower targeted tissue or cell specific delivery of the drug using the encapsulating vehicle as targeting and controlled release platform. 7-Ethyl-10-hydroxycamptothecin (SN-38) is an active metabolite of Irinotecan, showing 100- fold to 1000-fold higher effect than Irinotecan, but its clinical use is limited because of its extreme hydrophobicity, as it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. Method. In order to fully exploit the potential of the nanoprecipitation as a method for preparation of Poly(DL-lactide-co-caprolactone)- poly(ethylene oxide) - poly(propylene oxide) - poly(ethylene oxide) (P(DL)LCL/PEO-PPO-PEO) nanoparticles and evaluate the influence of the polymer P(DL)LCL, stabilizing agent PEO-PPO-PEO copolymer (Lutrol F127) and the drug concentration (SN-38) upon drug entrapment efficiency, size and drug content, a D-optimal experimental design for response surface using Design Expert Version 9.0.4.1. software investigation was created and statistically analyzed. Results. We have observed that at higher SN-38 concentration during the preparation procedure (nanoprecipitation, solvent diffusion method), and due to its extremely low water solubility, the drug will start to precipitate as unprotected crystals at a faster pace compared to polymer aggregation, leading to extremely low encapsulation efficacy and waste of the active compound. The most desirable combination of factor settings are SN-38=0.5 mg, Polymer=5mg and F127=4%. Conclusion. This investigation utilizes the design of experiment approach and extends the primary understanding of impact of formulation development of P(DL)LCL/PEO-PPO-PEO nanoparticles as carriers for SN-38.

Floating microspheres of Miglitol as gastro retentive drug delivery system: 32 full factorial design and in vitro evaluation

Background: The goal of this study was to develop a gastro retentive floating drug delivery system that would improve site specific activity, patient compliance and therapeutic efficacy.Methodology: Floating microspheres of Miglitol were formulated by double emulsion method using ethyl cellulose and eudragit E100 different weight ratio and PVA as an emulsifier. It has been prepared with respect quantity of polymer concentration and stirring speed to evaluate for % buoyancy, drug entrapment efficiency, particle size drug release rate. Result: The percent of buoyancy, drug entrapment efficiency, particle size, and percentage yield were increased with increase the polymer mixture concentration. Among all formulation batches, F6 showed acceptable results drug entrapment efficiency (86.57%) and buoyancy (94.25%). F10 formulation was prepared to check the predicted and actual factors and compared with optimized formulation F6. The drug release was increased as the polymer concentration was decrease. The kinetic model zero order had the highest regression coefficient value, it was described as a sustained release dosage form. According to ICH guideline accelerated stability studies of F6 and F10 formulations were conducted for 90 days. After 90 days buoyancy and in vitro drug release was performed and the results were F6 and F10 buoyancy was found to be 88.21%, 87.22% and in vitro drug release was found to be 62.87%, 63.51%. Conclusion: The present study, showed compatibility of drug with polymers by FTIR in formulation. Floating microsphere of Miglitol was prepared by double emulsion technique. The F6 Miglitol floating microsphere was optimized formulation demonstrated with excellent drug entrapment performance (86.57%), good floating behaviour (94.25%), and the largest particle size (670µm). The present study concludes that floating based gastro retentive delivery system of Miglitol microspheres has a safe and effective drug delivery system with increased therapeutic efficacy and a longer duration of action.

Development and evaluation of Pharmacosome formulations of Mefenamic acid

Patience who suffered from menstrual pain disease is generally prescribed the non-steroidal anti-inflammatory drug (NSAIDs). Monorrhagia or another blood disorder & some gynecological disorder, which impairs body function and acts as an economic burden. Due to respective use of ACE by oral route, it may cause GI complication such as bleeding, pain, perforation, abdominal pain, and swelling. To decrease the side effect of ACE, it is given by topical route in promotes the safety & efficacy of the ACE. The Mefenamic Acid pharmacosomes were prepared by the hand shaking method technique and evaluated by various methods such as in-vitro release study, % yield, drug entrapment efficiency, pH of the prepared formulation. The prepared system was also characterized by FTIR spectrophotometer to identify the drug-excipients interaction. The maximum entrapment efficiency of pharmacosomes was found to be 90%. The main aim of this study was to develop and characterized a vesicular drug carrier system for topical delivery of Mefenamic Acid to overcome the problem related with oral route.

Polymeric Fe3O4 Conjugates with Bioactive Plant Molecules: Platforms for Antimicrobial Therapy

The emerging nano biosystems are competent in diagnosis, drug delivery, and monitoring of therapeutic response. Both imaging and therapeutic functions can be achieved by using nanoplatforms. These nanoplatforms promise to revolutionize the medical management of many personalized illnesses. The well-developed surface chemistry of iron oxide (Fe3O4) makes it easy to charge them with pharmaceutics, promoting them as nanoplatforms for building up nanoparticle-based drug delivery systems. The strategy to design multifunctional Fe3O4 conjugates with bioactive molecules of plant origin to show enhanced activity is reported here. The conjugation reveals the magnetic Fe3O4 core nanoparticle surface readily link to hydroxyl sites of the Dextrin molecule, which further conjugate to conjugated with Curcumin and D-Limonene, which are powerful anti-cancer, anti-inflammatory, and antioxidant agents. The structural, morphological, optical, and magnetic properties were analyzed by X-ray diffraction, FT-Infrared, HR-Tunneling Electron Microscopy, and Vibrating Sample Magnetometer techniques. The potential drug loading was measured as Drug Entrapment Efficiency using UV-Vis spectroscopy. The antibacterial property was tested on the bacterium S. aureus and E. coli. Fe3O4-Dextrin nanoconjugates proved to be efficient for loading and stabilizing Curcumin and Limonene. Thus, multifunctional Fe3O4 conjugates are explored as exciting nano-drug carriers for targeted drug delivery.

Characterization of alginate extracted from Sargassum latifolium and its use in Chlorella vulgaris growth promotion and riboflavin drug delivery

Alginates derived from macroalgae have been widely used in a variety of applications due to their stability, biodegradability and biocompatibility. Alginate was extracted from Egyptian Sargassum latifolium thallus yielding 17.5% w/w. The chemical composition of S. latifolium is rich in total sugars (41.08%) and uronic acids (47.4%); while, proteins, lipids and sulfates contents are 4.61, 1.13 and 0.09%, respectively. NMR, FTIR and TGA analyses were also performed. Crystallinity index (0.334) indicates alginate semicrystalline nature. Sodium alginate hydrolysate was evaluated as Chlorella vulgaris growth promoter. The highest stimulation (0.7 g/L biomass) was achieved by using 0.3 g/L alginate hydrolysate supplementation. The highest total soluble proteins and total carbohydrates were 179.22 mg/g dry wt and 620.33 mg/g dry wt, respectively. The highest total phenolics content (27.697 mg/g dry wt.), guaiacol peroxidase activity (2.899 µmol min−1 g−1) were recorded also to 0.3 g/L alginate hydrolysate supplementation. Riboflavin-entrapped barium alginate-Arabic gum polymeric matrix (beads) was formulated to achieve 89.15% optimum drug entrapment efficiency (EE%). All formulations exhibited prolonged riboflavin release over 120 min in simulated gastric fluid, followed Higuchi model (R2 = 0.962–0.887) and Korsmeyer–Peppas model with Fickian release (n ranges from 0.204 to 0.3885).

Formulation and Evaluation of Ranitidine Hydrochloride Loaded Floating Microspheres for the Treatment of Gastric Ulcer

The study was aimed to prepare gastro retentive floating microsphere of Ranitidine Hydrochloride by Ionotropic Gelation technique and solvent evaporation technique by using the different carriers’ ratios (Carbopol 934, Chitosan, and sodium alginate). Both natural and synthetic polymers have been used to prepare floating microspheres and evaluated the relevant parameters. There was no drug and carrier interactions assessed from FTIR. Depending upon the ratio, the percentage yield was found between 58.33% to 90.38%. in all formulations. The surface morphology of microspheres was characterized by SEM and it was discrete, spherical in shape with rough outer surface and showed free flowing properties. The mean particle size of microspheres significantly increases with increasing polymer concentration and the range between 99.92±1.221 to 168.23±1.963 µm. Among all the formulations, RF3 showed high drug entrapment efficiency (87.52%). The percentage in-vitro buoyancy of the floating microspheres was in the range of 66.92% to 81.52%. The in-vitro drug release study revealed that RF3, RF6 and RF9 Formulations having 89.97%,92.91%,93.68% drug released at the end of dissolution studies respectively. It could be concluded that the developed floating microsphere of Ranitidine Hydrochloride can be used for prolonged release in stomach. Therefore improving the bioavailability and patient compliance.

DESIGN, DEVELOPMENT AND IN VITRO EVALUATION OF ERLOTINIB LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES BY BOX BEHNKEN DESIGN

Objective: To formulate and evaluate Erlotinib loaded Liquorice crude protein (LCP) nanoparticles from the powdered liquorice root (Glycyrrhiza glabra) using Box-Behnken design. Methods: Erlotinib loaded liquorice crude protein nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) and gluteraldehyde (8% v/v) as cross linking agent. Box-Behnken design with 3 factors, 3 levels and 3 responses was used to optimize the prepared nanoparticles. The independent variables were taken as A) Erlotinib concentration B) LCP concentration and C) Incubation time with responses R1) Drug entrapment efficiency R2) Drug Release and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, and in vitro drug release studies in PBS pH 7.4 (26 h) were carried out. The experimental values were found to be in close resemblance with the predicted value obtained from the optimization process. The in vitro cytotoxicity studies of the prepared nanoparticles in lung cancer cell line (A 549) were studied with different concentrations for 24h. Results: The average particle size, zeta potential, Polydispersity index (PDI) were found to be 292.1 nm,-25.8 mV and 0.384 respectively. TEM image showed that the nanoparticles dispersed well with a uniform shape and showed not much change during storage. The in vitro drug release showed 41.23% for 26 h in PBS (7.4) and release kinetics showed highest R2value (0.982) for Korsmeyer-Peppas model, followed by 0.977 for Higuchi model. The in vitro cytotoxicity of prepared nanoparticles in A 549 cell line showed good results with different concentrations for 24h. Conclusion: Erlotinib (Erlo) is a BCS class II drug with poor solubility, poor bioavailability and selective tyrosine kinase inhibitor for non small-cell lung cancer (NSCLC) through oral administration. To improve the oral bioavailability and absorption of molecules, plant protein as carriers is used for developing drug delivery systems due to their proven safety. The optimization variables were Conc of Erlo, Conc. of LCP and Incubation time to get responses as drug entrapment efficiency, drug release and particle size. The compatibility between drug and LCP were evaluated by FTIR.