Search results for: drug release model

Authors: Friday G. Okibe, Edit B. Agbaji, Victor O. Ajibola, Christain C. Onoyima

Abstract:

Controlled drug delivery systems reduce dose-dependent toxicity associated with potent drugs, including anticancer drugs. In this research, hydroxyapatite (HA) and hydroxyapatite-sodium alginate nanocomposites (HASA) were successfully prepared and characterized using Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The FTIR result showed absorption peaks characteristics of pure hydroxyapatite (HA), and also confirmed the chemical interaction between hydroxyapatite and sodium alginate in the formation of the composite. Image analysis from SEM revealed nano-sized hydroxyapatite and hydroxyapatite-sodium alginate nanocomposites with irregular morphologies. Particle size increased with the formation of the nanocomposites relative to pure hydroxyapatite, with no significant change in particles morphologies. Drug loading and in-vitro drug release study were carried out using synthetic body fluid as the release medium, at pH 7.4 and 37 °C and under perfect sink conditions. The result shows that drug loading is highest for pure hydroxyapatite and decreased with increasing quantity of sodium alginate. However, the release study revealed that HASA-5%wt and HASA-20%wt presented better release profile than pure hydroxyapatite, while HASA-33%wt and HASA-50%wt have poor release profiles. This shows that Methotrexate-loaded hydroxyapatite-sodium alginate if prepared under optimal conditions is a potential carrier for effective delivery of Methotrexate.

Keywords: drug-delivery, hydroxyapatite, methotrexate, nanocomposites, sodium alginate

Procedia PDF Downloads 244

Authors: Shaker Alsharif, Xavier Banquy

Abstract:

Controlled drug delivery technology represents one of the most rapidly advancing areas of science in which chemists and chemical engineers are contributing to human health care. Such delivery systems provide numerous advantages compared to conventional dosage forms including improved efficacy, and improved patient compliance and convenience. Such systems often use synthetic polymers as carriers for the drugs. As a result, treatments that would not otherwise be possible are now in conventional use. The role of bilayered vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the site avoidance and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. Our project focuses on developing and building hydrogel with nanoinclusion of liposomes loaded with active compounds such as proteins and growth factors able to release them in a controlled fashion. In order to achieve that, we synthesize several liposomes of two different phospholipids concentrations encapsulating model drug. Then, formulating hydrogel with specific mechanical properties embedding the liposomes to manage the release of active compound.

Keywords: controlled release, hydrogel, liposomes, active compounds

Procedia PDF Downloads 418

Authors: Dada Kolawole Segun

Abstract:

Transdermal drug delivery has gained popularity as a non-invasive method for controlled drug release compared to traditional delivery routes. Dissolvable transdermal patches have emerged as a promising platform for delivering a variety of drugs due to their ease of use. The objective of this research was to create and characterize dissolvable transdermal patches using various compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. A micromolding technique was utilized to fabricate the patches, which were subsequently characterized using scanning electron microscopy, atomic force microscopy, and tensile strength testing. In vitro drug release studies were conducted to evaluate the drug release kinetics of the patches. The study found that the mechanical strength and dissolution properties of the patches were influenced by the hyaluronic acid and zinc oxide nanoparticle ratios used in the fabrication process. Moreover, the patches demonstrated controlled delivery of model drugs through the skin, highlighting their potential for transdermal drug delivery applications. The results suggest that dissolvable transdermal patches can be tailored to meet specific requirements for drug delivery applications using different compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. This development has the potential to improve treatment outcomes and patient compliance in various therapeutic areas.

Keywords: transdermal drug delivery, characterization, skin permeation, biodegradable materials

Procedia PDF Downloads 53

Authors: Cesar Torres, Robert Briber, Nam Sun Wang

Abstract:

Eye drops are the most commonly used treatment for short-term and long-term ophthalmic diseases. However, eye drops could deliver only about 5% of the functional ingredients contained in a burst dosage. To address the limitations of eye drops, the use of therapeutic contact lenses has been introduced. Drug-loaded contact lenses provide drugs a longer residence time in the tear film and hence, decrease the potential risk of side effects. Nevertheless, a major limitation of contact lenses as drug delivery devices is that most of the drug absorbed is released within the first few hours. This fact limits their use for extended release. The present study demonstrates the application of long-alkyl chain ionic surfactants on extending drug release kinetics from commercially available silicone hydrogel contact lenses. In vitro release experiments were carried by immersing drug-containing contact lenses in phosphate buffer saline at physiological pH. The drug concentration as a function of time was monitored using ultraviolet-visible spectroscopy. The results of the study demonstrate that release kinetics is dependent on the ionic surfactant weight percent in the contact lenses, and on the length of the hydrophobic alkyl chain of the ionic surfactants. The use of ionic surfactants in contact lenses can extend the delivery of drugs from a few hours to a few weeks, depending on the physicochemical properties of the drugs. Contact lenses embedded with ionic surfactants could be potential biomaterials to be used for extended drug delivery and in the treatment of ophthalmic diseases. However, ocular irritation and toxicity studies would be needed to evaluate the safety of the approach.

Keywords: contact lenses, drug delivery, controlled release, ionic surfactant

Procedia PDF Downloads 114

Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

Abstract:

Drug dosage forms consisting of multi-unit particle systems (MUPS) for modified drug release provide a promising route for overcoming the limitation of conventional tablets. Despite the conventional use of pellets as units for MUP systems, 3D printed polymers loaded with a drug seem like an interesting candidate due to the control over dosing that 3D printing mechanisms offer. Further, 3D printing offers high flexibility and control over the spatial structuring of a printed object. The final MUPS tablets include PVP and HPC as granulate with other excipients, enabling the compaction process of this mixture with 3D printed inclusions, also termed minitablets. In this study, we have developed the multi-step production process for MUPS tablets, including the 3D printing technology. The MUPS tablets with incorporated 3D printed minitablets are a complex system for drug delivery, providing modified drug release. Such structured tablets promise to reduce drug fluctuations in blood, risk of local toxicity, and increase bioavailability, resulting in an improved therapeutic effect due to the fast transfer into the small intestine, where particles are evenly distributed. Drug loaded 3D printed minitablets were compacted into the excipient mixture, influencing drug release through varying parameters, such as minitablets size, matrix composition, and compaction parameters. Further, the mechanical properties and morphology of the final MUPS tablets were analyzed as many properties, such as plasticity and elasticity, can significantly influence the dissolution profile of the drug.

Keywords: 3D printing, dissolution kinetics, drug delivery, hot-melt extrusion

Procedia PDF Downloads 65

Authors: Monika Patel, Kazuaki Matsumura

Abstract:

Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

Procedia PDF Downloads 178

Authors: Jinfeng Zhang, Chun-Sing Lee

Abstract:

The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed for improving their drug loading capacities (typically less than 10%) and reducing their potential systemic toxicity. So development of alternative self-carried nanodrug delivery strategies without using any inert carriers is highly desirable. In this study, we developed a self-carried theranostic curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environment, with drug loading capacity higher than 78 wt.%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescent “OFF-ON” activation and real-time monitoring of Cur molecule release, showing its potential for cancer diagnosis. In vitro and in vivo experiments clearly show that therapeutic efficacy of the PEGylated Cur NPs is much better than that of free Cur. This self-carried theranostic strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and diagnosis.

Keywords: drug delivery, in vitro and in vivo cancer therapy, real-time monitoring, self-carried

Procedia PDF Downloads 373

Authors: Sharjeel Abid, Tanveer Hussain, Ahsan Nazir, Abdul Zahir, Nabyl Khenoussi

Abstract:

Localized application of drug has various advantages and fewer side effects as compared with other methods. Burn patients suffer from swear pain and the major aspects that are considered for burn victims include pain and infection management. Nano-fibers (NFs) loaded with drug, applied on local wound area, can solve these problems. Therefore, this study dealt with the fabrication of drug loaded NFs for better pain management. Two layers of NFs were fabricated with different drugs. Contact layer was loaded with Gabapentin (a nerve painkiller) and the second layer with acetaminophen. The fabricated dressing was characterized using scanning electron microscope, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction and UV-Vis Spectroscopy. The double layered based NFs dressing was designed to have both initial burst release followed by slow release to cope with pain for two days. The fabricated nanofibers showed diameter < 300 nm. The liquid absorption capacity of the NFs was also checked to deal with the exudate. The fabricated double layered dressing with dual drug loading and release showed promising results that could be used for dealing pain in burn victims. It was observed that by the addition of drug, the size of nanofibers was reduced, on the other hand, the crystallinity %age was increased, and liquid absorption decreased. The combination of fast nerve pain killer release followed by slow release of non-steroidal anti-inflammatory drug could be a good tool to reduce pain in a more secure manner with fewer side effects.

Keywords: pain management, burn wounds, nano-fibers, controlled drug release

Procedia PDF Downloads 225

Authors: Dipali Nagaonkar, Mahendra Rai

Abstract:

Chitosan, a carbohydrate polymer at nanoscale level has gained considerable momentum in drug delivery applications due to its inherent biocompatibility and non-toxicity. However, conventional synthetic strategies for chitosan nanoparticles mainly rely upon physicochemical techniques, which often yield chitosan microparticles. Hence, there is an emergent need for development of controlled synthetic protocols for chitosan nanoparticles within the nanometer range. In this context, we report the green synthesis of size controlled chitosan nanoparticles by using Pongamia pinnata (L.) leaf extract. Nanoparticle tracking analysis confirmed formation of nanoparticles with mean particle size of 85 nm. The stability of chitosan nanoparticles was investigated by zetasizer analysis, which revealed positive surface charged nanoparticles with zeta potential 20.1 mV. The green synthesized chitosan nanoparticles were further explored for encapsulation and controlled release of antioxidant biomolecule, quercetin. The resulting drug loaded chitosan nanoparticles showed drug entrapment efficiency of 93.50% with drug-loading capacity of 42.44%. The cumulative in vitro drug release up to 15 hrs was achieved suggesting towards efficacy of green synthesized chitosan nanoparticles for drug delivery applications.

Keywords: Chitosan nanoparticles, green synthesis, Pongamia pinnata, quercetin

Procedia PDF Downloads 550

Authors: Venkatalakshmi Ranganathan, Ong Hsin Ju, Tan Yinn Ming, Lim Kien Sin, Wong Man Ting, Venkata Srikanth Meka

Abstract:

The mucoadhesive buccal tablet is an oral drug delivery system which attached to the buccal surface for direct drug absorption into the systemic circulation and the unidirectional drug release is ensured by formulating a hydrophobic backing layer. The objective of present study was to formulate mucoadhesive atenolol bilayer buccal tablets by using sodium alginate, hydroxyethyl cellulose, and xanthan gum as mucoadhesive polymer and the technique applied was direct compression method. Ethyl cellulose was used as backing layer of the tablet. FTIR and DSC analysis were carried out to identify the drug polymer interactions. The prepared tablets were evaluated for physicochemical parameters, ex vivo mucoadhesion time and in-vitro drug release. The formulated tablets showed the average surface pH 6-7 which is favourable for oral mucosa. The formulation containing sodium alginate showed more than 90 % of drug release at the end of the 7 hours in vitro dissolution studies. The formulation containing xanthan gum showed more than 8 hours of mucoadhesion time and all formulation exhibited non fickian release kinetics. The present study indicates enormous potential of erodible mucoadhesive buccal tablet containing atenolol for systemic delivery with an added advantage of circumventing the hepatic first pass metabolism.

Keywords: atenolol, mucoadhesion, in vitro drug release, direct compression, ethyl cellulose

Procedia PDF Downloads 595

Authors: Nagasamy Venkatesh Dhandapani

Abstract:

This work aims at investigating the use of β-Cyclodextrin as a cross linker, in an attempt to formulate nanosponges containing ketoconazole. The nanosponges were prepared by cross-linking method. The excipients used in this study did not alter the physicochemical properties of a drug as revealed by FTIR spectroscopy. Studies on various formulation variables revealed that all the variables are inter-related with the formulation. The ideal batch among the formulation was selected based on the higher entrapment efficiency and drug loading. The in vitro release studies of ketoconazole nanosponges in hydrogel exhibited a sustained release over a period of 24 hours. Mathematical analysis of drug release from the formulation followed non-Fickian diffusion obeying first order kinetics. The anti-fungal activity of the formulation exhibited better zone of inhibition when compared to pure drug (ketoconazole) against Tinea corporis.

Keywords: nanosponges, beta-cyclodextrin, ketoconazole, tinea corporis

Procedia PDF Downloads 121

Authors: Rashi Rajput, Manisha Singh

Abstract:

Escitalopram oxalate (ETP), an FDA approved antidepressant drug from the category of SSRI (selective serotonin reuptake inhibitor) and is used in treatment of general anxiety disorder (GAD), major depressive disorder (MDD).When taken orally, it is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT) in the liver with the help of enzymes CYP2C19, CYP3A4 and CYP2D6. Hence, causing side effects such as dizziness, fast or irregular heartbeat, headache, nausea etc. Therefore, targeted and sustained drug delivery will be a helpful tool for increasing its efficacy and reducing side effects. The present study is designed for formulating mucoadhesive nanoparticle formulation for the same Escitalopram loaded polymeric nanoparticles were prepared by ionic gelation method and characterization of the optimised formulation was done by zeta average particle size (93.63nm), zeta potential (-1.89mV), TEM (range of 60nm to 115nm) analysis also confirms nanometric size range of the drug loaded nanoparticles along with polydispersibility index of 0.117. In this research, we have studied the in vitro drug release profile for ETP nanoparticles, through a semi permeable dialysis membrane. The three important characteristics affecting the drug release behaviour were – particle size, ionic strength and morphology of the optimised nanoparticles. The data showed that on increasing the particle size of the drug loaded nanoparticles, the initial burst was reduced which was comparatively higher in drug. Whereas, the formulation with 1mg/ml chitosan in 1.5mg/ml tripolyphosphate solution showed steady release over the entire period of drug release. Then this data was further validated through mathematical modelling to establish the mechanism of drug release kinetics, which showed a typical linear diffusion profile in optimised ETP loaded nanoparticles.

Keywords: ionic gelation, mucoadhesive nanoparticle, semi-permeable dialysis membrane, zeta potential

Procedia PDF Downloads 268

Authors: Surendra Agrawal, Pravina Gurjar, Supriya Bhide, Ram Gaud

Abstract:

Levamisole hydrochloride is a prominent anticancer drug in the treatment of colon cancer but resulted in toxic effects due poor bioavailability and poor cellular uptake by tumor cells. Levamisole is an unstable drug. Incorporation of this molecule in solid lipids may minimize their exposure to the aqueous environment and partly immobilize the drug molecules within the lipid matrix-both of which may protect the encapsulated drugs against degradation. The objectives of the study were to enhance bioavailability by sustaining drug release and to reduce the toxicities associated with the therapy. Solubility of the drug was determined in different lipids to select the components of Solid Lipid Nanoparticles (SLN). Pseudoternary phase diagrams were created using aqueous titration method. Formulations were subjected to particle size and stability evaluation to select the final test formulations which were characterized for average particle size, zeta potential, and in-vitro drug release and percentage transmittance to optimize the final formulation. SLN of Levamisole hydrochloride was prepared by Nanoprecipitation method. Glyceryl behenate (Compritol 888 ATO) was used as core comprising of Tween 80 as surfactant and Lecithin as co-surfactant in (1:1) ratio. Entrapment efficiency (EE) was found to be 45.89%. Particle size was found in the range of 100-600 nm. Zeta potential of the formulation was -17.0 mV revealing the stability of the product. In-vitro release study showed that 66 % drug released in 24 hours in pH 7.2 which represent that formulation can give controlled action at the intestinal environment. In pH 5.0 it showed 64% release indicating that it can even release drug in acidic environment of tumor cells. In conclusion, results revealed SLN to be a promising approach to sustain the drug release so as to increase bioavailability and cellular uptake of the drug with reduction in toxic effects as dose has been reduced with controlled delivery.

Keywords: SLN, nanoparticulate delivery of levamisole, pharmacy, pharmaceutical sciences

Procedia PDF Downloads 403

Authors: Krutika K. Sawant, Anil Solanki

Abstract:

The present study deals with the preparation and optimization of ethyl cellulose-containing disopyramide phosphate loaded microspheres using solvent evaporation technique. A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for optimizing the preparation microspheres. The drug:polymer ratio (X1) and speed of the stirrer (X2) were chosen as the independent variables. The cumulative release of the drug at a different time (2, 6, 10, 14, and 18 hr) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable at time 10 hr. Based on the results of multiple linear regression analysis and F statistics, it was concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. The drug release pattern fitted the Higuchi model well. The data of a selected batch were subjected to an optimization study using Box-Behnken design, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Keywords: disopyramide phosphate, ethyl cellulose, microspheres, controlled release, Box-Behnken design, factorial design

Procedia PDF Downloads 429

Authors: Surajj Sarode, G. P. Vadnere, G. Vidya Sagar

Abstract:

Compression coating is one of the strategies for delivering drug to the colon based on Gastrointestinal PH and transit time concept. The main aim of these formulations to develop rapidly disintegrating Zaltoprofen core tablets compression-coated with a mixture of time-dependent hydrophilic swellable polymer HPMC K 15 and PH responsive soluble polymer Chitosan and Guar gum in different ratios. The effect of the proportion of HPMC, Chitosan and Guar gum in the coat on premature drug release in upper part (Stomach and small intestine) of GIT and the amount of drug release in colon target area was studied. The formulations are carried out by using Direct Compression method. Sodium starch Glycolate used for rapid disintegration. FTIR used for Drug-Polymer Interaction studies. The prepared tablets were evaluated for hardness, thickness, friability, in-vitro disintegration, in-Vitro dissolution and in-vitro kinetic study.

Keywords: zaltoprofen, chitosan, formulation, drug delivery

Procedia PDF Downloads 423

Authors: Chieh-Nan Chen, Ji-Yu Lin, I-Ming Chu

Abstract:

Polypeptide thermosensitive hydrogel is an excellent candidate as a smart device to deliver drugs and cells due to its remarkable biocompatibility, low gelation concentration, and respond to temperature stimuli, it can be easily injected as a polymer solution into the patient’s body where it undergoes gelation due to an elevation in temperature. Poly (ethylene glycol) monomethyl ether-poly (ethyl-l-glutamate) (mPEG-PELG) contains a hydrophobic side chain –C2H5 which is useful in encapsulating and stabilizing hydrophobic drugs. In this study, we plan to focus on the hydrophobic anti-carcinogenic and anti-inflammatory drug curcumin, which due its insolubility in water, requires a proper carrier for delivery into the body. Our main concept is to use mPEG-PELG to stabilize curcumin, inject the curcumin-loaded hydrogel into the tumor site, and allow the enzymatically-sensitive hydrogel to be degraded by bodily fluids and release the drug. The polymers of interest have been successfully synthesized and characterized by 1H-NMR, FT-IR, SEM, and CMC. Curcumin loading content and drug release were assayed using HPLC. Preliminary results show that these materials have potential as a delivery vehicle for poorly soluble drugs.

Keywords: curcumin, drug release, hydrogel, polypeptide material

Procedia PDF Downloads 272

Authors: Naima Bouslah, Leila Bounabi, Farid Ouazib, Nabila Haddadine

Abstract:

Conventional release dosage forms are known to provide an immediate release of the drug. Controlling the rate of drug release from polymeric matrices is very important for a number of applications, particularly in the pharmaceutical area. Hydrogels are polymers in three-dimensional network arrangement, which can absorb and retain large amounts of water without dissolution. They have been frequently used to develop controlled released formulations for oral administration because they can extend the duration of drug release and thus reduce dose to be administrated improving patient compliance. Tramadol is an opioid pain medication used to treat moderate to moderately severe pain. When taken as an immediate-release oral formulation, the onset of pain relief usually occurs within about an hour. In the present work, we synthesized pH-responsive hydrogels of (hydroxyl ethyl methacrylate-co-acrylic acid), (HEMA-AA) for control drug delivery of tramadol in the gastro-intestinal tractus. The hydrogels with different acrylic acid content, were synthesized by free radical polymerization and characterized by FTIR spectroscopy, X ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). FTIR spectroscopy has shown specific hydrogen bonding interactions between the carbonyl groups of the hydrogels and hydroxyl groups of tramadol. Both the XRD and DSC studies revealed that the introduction of tramadol in the hydrogel network induced the amorphization of the drug. The swelling behaviour, absorptive kinetics and the release kinetics of tramadol in simulated gastric fluid (pH 1.2) and in simulated intestinal fluid (pH 7.4) were also investigated. The hydrogels exhibited pH-responsive behavior in the swelling study. The (HEMA-AA) hydrogel swelling was much higher in pH =7.4 medium. The tramadol release was significantly increased when pH of the medium was changed from simulated gastric fluid (pH 1.2) to simulated intestinal fluid (pH 7.4). Using suitable mathematical models, the apparent diffusional coefficients and the corresponding kinetic parameters have been calculated.

Keywords: biopolymres, drug delivery, hydrogels, tramadol

Procedia PDF Downloads 332

Authors: Gajera Lalit, Shah Pranav, Shah Shailesh

Abstract:

Venlafaxine hydrochloride has a short elimination half-life of 5 ± 2 hr, and absorption window in the upper part of gastrointestinal tract. The conventional tablets need to be administered two to three times a day and possess an oral bioavailability of 45%. The purpose of this study was to formulate gastroretentive effervescent floating tablets of Venlafaxine HCl. Different grades of HPMC namely K15M, K4M, K100M and E15LV were employed as swelling polymers whereas sodium bicarbonate was employed as gas generating agent. The direct compression method was employed for the formulation of tablets. The tablets were evaluated in terms of hardness, friability, weight variation, drug content, water uptake, in-vitro floating behavior and in-vitro drug release study. All the formulations exhibited very short floating lag time of < 1 min and total floating time of 12 hr. Formulation L3 containing 25 mg and 75 mg of HPMC E15 LV and HPMC K15M respectively exhibited complete drug release within 12 hrs.

Keywords: venlafaxine HCl, hydroxyl propyl methylcellulose, floating gastro retentive tablets, in-vitro drug release, non-fickian diffusion

Procedia PDF Downloads 508

Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

Abstract:

Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

Procedia PDF Downloads 93

Authors: S. T. Kumbhar, M. S. Bhatia, R. C. Khairate

Abstract:

An effective nanodrug delivery system was developed by using chitosan for increased encapsulation efficiency and retarded release of curcumin. Potential ionotropic gelation method was used for the development of chitosan nanoparticles with TPP as cross-linker. The characterization was done for analysis of size, structure, surface morphology, and thermal behavior of synthesized chitosan nanoparticles. The encapsulation efficiency was more than 80%, with improved drug loading capacity. The in-vitro drug release study showed that curcumin release rate was decreased significantly. These chitosan nanoparticles could be a suitable platform for co-delivery of curcumin and anticancer agent for enhanced cytotoxic effect on tumor cells.

Keywords: Curcumin, chitosan, nanoparticles, anticancer activity

Procedia PDF Downloads 147

Authors: Filipa Vasconcelos

Abstract:

The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.

Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes

Procedia PDF Downloads 78

Authors: M. Kumpugdee-Vollrath, J.-P. Krause, S. Bürk

Abstract:

Most of the drugs used for pharmaceutical purposes are poorly water-soluble drugs. About 40% of all newly discovered drugs are lipophilic and the numbers of lipophilic drugs seem to increase more and more. Drug delivery systems such as nanoparticles, micelles or liposomes are applied to improve their solubility and thus their bioavailability. Besides various techniques of solubilization, oil-in-water emulsions are often used to incorporate lipophilic drugs into the oil phase. To stabilize emulsions surface active substances (surfactants) are generally used. An alternative method to avoid the application of surfactants was of great interest. One possibility is to develop O/W-emulsion without any addition of surface active agents or the so called “surfactant-free emulsion or SFE”. The aim of this study was to develop and characterize SFE as a drug carrier by varying the production conditions. Lidocaine base was used as a model drug. The injection method was developed. Effects of ultrasound as well as of temperature on the properties of the emulsion were studied. Particle sizes and release were determined. The long-term stability up to 30 days was performed. The results showed that the surfactant-free O/W emulsions with pharmaceutical oil as drug carrier can be produced.

Keywords: emulsion, lidocaine, Miglyol, size, surfactant, light scattering, release, injection, ultrasound, stability

Procedia PDF Downloads 461

Authors: Blessing A. Aderibigbe

Abstract:

Combination therapy is a treatment approach that is used to prevent the emergence of drug resistance. This approach is used for the treatment of many chronic and infectious diseases. Potentiating agents are currently explored in combination therapy, resulting in excellent therapeutic outcomes. Breast cancer and malaria are two chronic conditions responsible globally for high death rates. In this research, a class of polymer-drug conjugates containing potentiating agents with either antimalarial or anticancer drugs were prepared by Michael Addition Polymerization reaction and ring-opening polymerization reaction. Conjugation of potentiating agents with bioactive compounds into the polymers resulted in conjugates with good water solubility, highly selective and non-toxic. In vitro cytotoxicity and in vitro antiplasmodial evaluation on the conjugates revealed that the conjugates were more effective when compared to the free drugs. The drug release studies further showed that the release profile of the drugs from the conjugates was sustained. The findings revealed the potential of polymer-drug conjugates to overcome drug toxicity and drug resistance, which is common with the currently used antimalarial and anticancer drugs.

Keywords: anticancer, antimalarials, combination therapy, polymer-drug conjugates

Procedia PDF Downloads 100

Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

Abstract:

This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

Procedia PDF Downloads 84

Authors: Zaheer Ahmad, Afzal Shah

Abstract:

pH responsive block copolymers consist of mPEG and glutamic acid units were syntheiszed in different formulations. The synthesized polymers were structurally investigated. Doxorubicin Hydrocholide (DOX-HCl) as a chemotherapy medication for the treatment of cancer was selected. DOX-HCl was loaded and their drug loading content and drug loading efficiency were determined. The nanocarriers were obtained in small size, well shaped and slightly negative surface charge. The release study was carried out both at pH 7.4 and 5.5 and it was revealed that the release was sustained and in controlled manner and there was no initial burst release. The in vitro release study was further carried out for different formulations with different glutamic acid moieties. Time dependent cell proliferation inhibition of the free drug and drug loaded nanoparticles against human breast cancer cell lines MCF-7 and Zr-75-30 was observed. Cellular uptakes and endocytosis were investigated by confocal laser scanning microscopy (CLSM) and flow cytometery. The biocompatibility, optimum size, shape and surface charge of the developed nanoparticles make the nanoparticles an efficient drug delivery carrier.

Keywords: doxorubicin, glutamic acid, cell proliferation inhibition, breast cancer cell

Procedia PDF Downloads 100

Authors: Nor Jannah Mohd Sebri, Khairul Anuar Mat Amin

Abstract:

Dication cross-linked gellan gum hydrogel loaded with Ibuprofen with excellent mechanical properties had been synthesized as potential candidate for non-toxic biocompatible polymer material in tissue engineering. The gellan gum hydrogel with 5% Ibuprofen had produced a slow release profile with total drug release time of 25 hours as a resulting low swelling value recorded at 22+0.5%. Its compressive strength, 200.13+21 kPa was highest of all other hydrogel ratio of 0.5% and 1.0% Ibuprofen incorporation. Young’s Modulus of the hydrogel with 5% Ibuprofen was recorded at 1.8+0.01 MPa, indicating good gel strength in which it is capable of withstanding a fair amount of subjected force during topical wound dressing application. Excellent mechanical properties, together with slow release profile, make the ibuprofen-loaded hydrogel a prospect candidate as biocompatible extracellular matrices in wound management.

Keywords: gellan gum, ibuprofen, slow drug release, hydrogel

Procedia PDF Downloads 363

Authors: Seyedeh Faranak Baniahmad, Soroor Yousefi

Abstract:

Osteoporosis is a bone disease which increases the bone fracture risk, reduces the bone mineral density (BMD) and alters the amount and variety of proteins in bones. Antiresorptive therapy is one the most popular Osteoporosis treatment methods. In this method the bisphosphonates, hormones, calcitonin or the selective estrogen receptor modulators is replaced. In order to reduce undesirable effects and to increase the bioavailability of drug agents, the controlled drug delivery systems have been utilized. In current study, the controlled release of Alendronate from LDH-PCL with (0, 5, 10, 15 % wt. of LDH) was investigated. The results showed that the release of alendronate from the lamellar LDH incorporated into the PCL matrix is much slower than the release of alendronate from the PCL. Therefore such systems are very promising, in which the antiresorptive drug has to remain in the matrix for longer time and can be released in controlled manner.

Keywords: osteoporosis, alendronate, poly (ε–caprolactone), layered double hydroxide

Procedia PDF Downloads 353

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

Abstract:

Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

Procedia PDF Downloads 305

Authors: Abhishek Kumar Sah, Preeti K. Suresh

Abstract:

Effective drug delivery to the eye is a massive challenge, due to complicated physiological ocular barriers, rapid washout by tear and nasolachrymal drainage. Thus, most of the conventional ophthalmic formulations face the problem of low ocular bioavailability. Ophthalmic drug therapy can be improved by enhancing the precorneal drug retention along with improved drug penetration. The aim of the present investigation was to develop and evaluate a biodegradable polymer poly (D, L-lactide-co-glycolide) (PLGA) coated nanoparticulate carrier of loteprednol etabonate. PLGA nanoparticles were prepared by modified emulsification/solvent diffusion method using high-speed homogenizer followed by sonication. The nanoparticles were characterized for various parameters such as particle size, zeta potential, polydispersity index, X-ray powder diffraction (XRD), Transmission electron microscopy (TEM), in vitro drug release profile and stability. The prepared nanocarriers displayed mean particle size in the range of 271.7 to 424.4 nm, with zeta potential less than –10 mV. In vitro release in simulated tear fluid (STF) nanocarrier showed an extended release profile of loteprednol etabonate. TEM confirmed the spherical morphology and smooth surface of the particles. All the prepared formulations were found to be stable at varying temperatures.

Keywords: drug delivery, ocular delivery, polymeric nanoparticles, loteprednol etabonate

Procedia PDF Downloads 513

Authors: Yaowaporn Sangsen, Kittisak Likhitwitayawuid, Boonchoo Sritularak, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

Abstract:

Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol® 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. In vitro drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system to develop for the oral OXY delivery.

Keywords: solid lipid nanoparticles, physicochemical properties, in vitro drug release, oxyresveratrol

Procedia PDF Downloads 368