Flaxseed Mucilage Hydrogel based Floating Drug Delivery System: Design and Evaluation

Objective: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are essential part of the administration of Rheumatoid Arthritis (RA). Methotrexate (MTX) is effective for tumor necrosis factor alpha (TNF-a) biologic agents, indicated only in minority of patients suffering from severe RA. MTX remains the "anchor drug" in the treatment of RA. For delivery improvement, novel pharmaceutical drug delivery system i.e. MTX-Cubosomes were developed.
 Methods: Poloxamer 407 and Glycerol monooleate (Monoelin, MO) used and the formulation were characterized as a sustained release drug delivery system for Methotrexate. Different ratios of Monolein, Poloxamer 407 and water were used to develop the different cubosomes using homogenization and emulsification method. Characterization of formulations for morphology was performed and also particle size distribution by Transmission Electron Microscopy (TEM).
 Results: Formulation showed the internal cubic structures of the vesicles. The particle size of the formulations was found to be ranging from 53.21 to 185.32 nm, zeta potential of the formulations varied from-18.20-36.10 mV. The cubosomal formulation exhibited good entrapment efficiency along with high drug loading. Compatibility with the excipients was also established. An in vitro release study was done using Franz Diffusion cell indicated sustained release of the formulation at a rate of 1.25 %/h. Cubosomes proved to be reliable system for sustained transdermal drug delivery system.
 Conclusion: Methotrexate cubosomes is a novel medication delivery framework and in this examination it has been developed and characterized. The formulations were found to be promising in terms of its characterization parameters like particle size, zeta potential, entrapment efficiency, loading capacity, release kinetics, and stability, suitable for topical delivery.

Nano-crystalline cellulose: Preparation, modification and usage as sustained release drug delivery excipient for some non-steroidal anti-inflammatory drugs

Lafutidine a newly developed histamine H2-receptor antagonist having biological half-life of 1.92 ± 0.94 h due to its selective absorption from upper part of gastrointestinal tract the development of mucoadhesive sustained release drug delivery system is recommended in order to enhance the bioavailability. A mucoadhesive tablets was developed using the natural polymer, sodium alginate, xanthan gum and karaya gum. Mucoadhesion is a complex phenomenon which involves wetting, adsorption and interpenetration of polymer chains. The prepared tablets of various formulations were evaluated for a total mucoadhesion time, buoyancy lag time and percentage drug released. The formulation with xanthan gum showed better results. Thus, it may be useful for prolonged drug release in stomach to improve the bioavailability and reduced dosing frequency. Non-fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer–Peppas. The optimized formulation (B3) showed a mucoadhesive strength >35 g. In vivo study was performed using rabbits by X-ray imaging technique. Radiological evidences suggest that, a formulated tablet was well adhered for >10 h in rabbit’s stomach. Optimized lafutidine mucoadhesive tablets showed no significant change in physical appearance, drug content, mucoadhesive properties and in vitro dissolution pattern after storage at 40 °C temperature 75 ± 5% relative humidity for 3 months.

Long-term drug delivery systems are an attractive option to drug manufacturers and patients alike due to simplified dosing schedules and reduced negative side effects which increase patient therapy compliance and quality of life. Being studied for decades, multiple controlled release systems have been developed to sustain the release of target therapeutic agents; however, these methods have various drawbacks such as difficulty in formulation, high cost, etc. that limit widespread commercial usage. One pervasive challenge in these solutions is the burst release phenomena-where an uncontrolled bolus of drug is released immediately upon product usage which lowers the effective lifetime of the drug or medical device. While methods have been developed to address burst release in sustained release systems, these methods often require extra processing steps that waste a portion of the initially loaded drug or may leave the device prone to failure if not processed correctly. To address this issue, a microfluidic release system was developed using a novel method of rapidly, tunably, and cost effectively creating microchannels bundles without the use of non-biocompatible materials. In this study, we investigated the sustained release of both a model small molecule and model large molecule from these novel microchannel bundles of varying channel diameters. From this, we discovered that rate of release was tunably controlled by modifying microchannel diameters in these bundles, significantly extending the product lifetime at increasingly thin channel diameters. Additionally, burst release was decreased by tunably lowering microchannel diameters within the bundle. As a result, this study provides a novel method of creating microfluidic drug delivery systems that could address major issues in current sustained release drug delivery systems.

Oral drug delivery system represents one of the main areas of sustained drug delivery system. Floating drug delivery system related to oral sustained drug delivery system group, which is capable of floating in the stomach for an exteneded period of time. Ranitidine hydrochloride is a histamine H2-receptor antagonist. It is widely prescribed in active duodenal ulcers, gastric ulcers, Zollinger-Ellison syndrome and GERD. A traditional oral sustained release formulation releases most of the drug at the colon, thus the drug should have absorption window either in the colon or throughout the gastrointestinal tract. Ranitidine is absorbed only in the initial part of the small intestine and has 50% absolute bioavailability. The aim of the present research is to provide a gastroretentive system for sustained release of Ranitidine hydrochloride in the upper part of the gastrointestinal tract in the form of floating tablet. Gastroretentive tablets of Ranitidine Hydrochloride were prepared by direct compression technique using polymers like Carbopol, Chitosan, Styrene-divinylbenzene and the mixture of Magnesium stearate as a lubricant, Talc as a glidant and Lactose as fillers. The results of the present research show that the chitosan and carbopol 940 mixed matrices can be used to modify release rates in hydrophilic matrix tablets prepared by direct compression. Incorporation of the highly porous low-density copolymer in the matrix tablets provides densities that are lower than the density of the release medium. 17% w/w low density copolymer (based on the mass of the tablet) was sufficient to achieve proper in vitro floating behavior for at least 8 h. Keywords: Floating drug delivery system, Ranitidine hydrochloride, Gastrointestinal tract, Carbopol, ChitosanÂ

pH-responsive and sustained release drug delivery system of BSA coated CDs-DOX

Oral route of drug administration is the most preferable route because of its flexibility in formulation, ease of administration, and patient compliance. But this route has certain limitations like limited gastric residence time (GRT) for sustained drug delivery system and for the drugs which are absorb from specific region of gastrointestinal tract (GIT). To overcome these limitations, various approaches have been proposed to increase the gastric retention time of the delivery system in the upper part of gastrointestinal tract. Gastroretentive dosage form (GRDF) prolongs the GRT by targeting site-specific drug release in upper part of GIT. GRDFs enable continuous and the extended duration of drug release and improve bioavailability of drugs that have narrow therapeutic window, by this way they prolong dosing interval and increase compliance of the patient. The purpose of this article is to compile the various gastroretentive approaches. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. Finally the evaluation parameters of gastroretentive drug delivery systems are covered. The present review addresses briefly about the current status of various leading gastroretentive drug delivery technologies, developed until now, i.e. high density (sinking), floating, bio- or mucoadhesive, expandable, unfoldable, super porous hydrogel, magnetic systems etc. In addition, important factors controlling gastroretention, advantages and finally, future potential are discussed.Keywords: Floating Delivery, Gastro retentive system.Â

Evaluating the link between self-assembled mesophase structure and drug release

Introduction Glaucoma is a group of progressive optic neuropathies resulting in irreversible blindness. It is associated with an elevation of intraocular pressure (>21 mm Hg) and optic nerve damage. Reduction of the intraocular pressure (IOP) through the administration of ocular hypotensive eye drops is one of the most common therapeutic strategies. Patient adherence to conventional eye drops remains a major obstacle in preventing glaucoma progression. Additional problems emerge from inadequate patient education as well as local and systemic side effects associated with adminstering ocular hypotensive drugs. Areas covered Sustained-release drug delivery systems for glaucoma treatment are classified into extraocular systems including wearable ocular surface devices or multi-use (immediate-release) eye formulations (such as aqueous solutions, gels; ocular inserts, contact lenses, periocular rings, or punctual plugs) and intraocular drug delivery systems (such as intraocular implants, and microspheres for supraciliary drug delivery). Expert opinion Sustained release platforms for the delivery of ocular hypotensive drugs (small molecules and biologics) may improve patient adherence and prevent vision loss. Such innovations will only be widely adopted when efficacy and safety has been established through large-scale trials. Sustained release drug delivery can improve glaucoma treatment adherence and reverse/prevent vision deterioration. It is expected that these approaches will improve clinical management and prognosis of glaucoma.

The main objective of sustained release drug delivery system is to provide a steady state blood plasma level concentration which is non-toxic and therapeutically active for a longer period of time. Owing its increased patient compliance and prolonged release of action in delivering drugs several benefits can be contemplated in delivering of sustained release dosage form[1]. Among various route of drug delivery Sustained release drug delivery is most widely preferred as it’s less frequency of dosing and controls the release of drugs. Natural polymers are biodegradable and nontoxic in nature with reduced side effects. It is also eco-friendly and safe to be administered as compared to synthetic polymers. The current work was based on preparation of sustained release tablets of Propranolol Hydrochloride using natural polymers like Gum Acacia, Hibiscus Rosasinesis and Microcrystalline cellulose. Presently much attention is being paid for formulation of sustained release tablets that contains matrix system. Direct compression method was used for formulation of sustained release tablets of Propranolol Hydrochloride. The prepared tablets were evaluated for different pre-formulation studies and in vitro dissolution studies were performed using USP-III dissolution apparatus. Dissolution studies of different formulations were evaluated for 24 hours at 370C.

Sustained release cellulose acetate (CA) and ethyl cellulose (EC) polymer blend nanofibers loaded with ketoprofen (KET) were successfully prepared by electrospinning. Successful fiber formation has been investigated by using two different binary solvent systems, i.e., acetic acid + distilled water (2:1 v/v) and acetone + N,N-DMAc + ethanol (2:1:1 v/v). Scanning electron microscopy (SEM) images showed that morphological features gradually change as the ratio of both polymers change. Nanofiber diameter also decreases as the CA content is increased in the polymer blend solution from 77.25 ±27 to 72.39 ±30 nm. Drug release profiles were evaluated by in-vitro drug release experiments. Drug release follows a pseudo-Fickian behavior of diffusion and shows a sustained release mechanism. Nanofibers containing more CA show greater controlled release capacity as compared to EC. X-ray diffraction (XRD) patterns of CA and EC polymer blend nanocomposites show that crystalline ketoprofen has changed into an amorphous state. Fourier transform Infrared (FTIR) analysis indicates hydrogen bonding occurs between the drug and the polymer, accounting for molecular integration of the two components. The thermal stability of the prepared polymer blend was also studied using thermo-gravimetric analysis (TGA). A polymer blend sustained release drug delivery system prepared by electrospinning make it possible to fabricate other novel drug releasing systems.

An oral medication of a molecular targeted drug, lapatinib, is taken regularly to maintain the drug concentration within the desired therapeutic levels. To alleviate the need for such cumbersome administration schedules in several drugs, advanced drug delivery systems (DDSs), which can provide time-controlled and sustained drug release, have recently received significant attention. A biodegradable synthetic polymer, such as polycaprolactone (PCL), is usually used as a carrier material for DDSs. In this paper, lapatinib powder-entrapped, PCL microstructures were fabricated with a precise X-ray lithography-based method. In vitro experiments on HER2 positive-human gastric cancer derived NCI-N87 cells were performed to appraise the drug release characteristics of the fabricated DDSs. The in vitro results indicate that after the X-ray lithography process, the lapatinib powder is still working well and show time- and dose- dependent drug release efficiencies. The cell growth inhibition characteristics of one hundred 40-μm sized microstructures were similar to those of a 1 μM lapatinib solution for over 144 h. In conclusion, the developed lapatinib-entrapped PCL microstructures can be used in molecular targeted delivery and sustained release as effective cancer-targeted DDSs.

Electrospinning is one of the most promising techniques for producing nanofibers for pharmaceutical and medical applications. Electrospun fibers are especially promising as sustained release drug delivery systems of biotherapeutics. However, a typical electrospinning system made of a single needle configuration has a low fiber production efficiency and throughput. Good candidates to overcome the low productivity issue are the needleless spinnerets. Many of them have already been experimentally and theoretically tested, but their comprehensive comparison is still needed. This study summarizes the most efficient needle-free electrospinning configurations based on their extensive electric field profile description simulated using the finite element method (FEM). Understanding these properties is crucial when choosing the electrospinning system that allows high-throughput production of the monodispersed nanofibers. The ability to control the process will enable its applications in drug delivery systems.

Background: Medicine is a substance that through its chemical effects brings about changes in biological functions. The GRDDS delivery system is a sustained drug delivery system that can hold drugs back in the stomach for a longer time. The advantages of GRDDS include being able to increase bioavailability, increase the solubility of drugs that are poorly soluble in high pH, can control of therapeutic levels to reduce the occurrence of fluctuations, can extend the half-life so that the frequency of drug administration can be reduced.
 
 Objectives: This study aims to describe the types of GRDDS preparations. The variation is due to a combination of differences in mechanisms and technology.
 
 Method: The design in this study uses a systematic review of the review process that identifies, assesses, and interprets all findings on a research topic.
 
 Result: Floating systems can use expandable polymeric materials such as HPMC and chitosan. The floating mechanism begins with the contact of gastric juices with tablets which causes the polymer to hydrate to form a gel layer that can withstand CO2 gas formed due to the interaction of sodium bicarbonate with citric acid so that the tablets can expand and can float. The oral drug delivery route is the most preferred because it is easy to use. Absorption of oral drugs mostly occurs in the stomach and the intestines.
 
 Conclusion: Therefore, it is necessary to have a drug delivery system that can extend the contact time with the stomach, namely the Gastroretentive Drug Delivery System (GRDDS).

Rebamipide is an amino acid analog of 2-(1H)-quinolinone used in the treatment of peptic ulcer. Here we sought to formulate and evaluate gastroretentive floating-bioadhesive tablets of rebamipide to increase the gastric residence time and further compare their pharmacokinetics with conventional immediate release tablets. Floating-bioadhesive tablets of rebamipide were prepared with combination of Polyox WSR 303 and CP 971P/HPMC K4M and Sodium CMC by direct compression method. The prepared formulations were evaluated for hardness, thickness, weight variation, friability, drug content, in vitro buoyancy and drug release. The optimized formulation (RBF12) floated with a lag time of 28.3 ± 3.2 sec, duration of floating 12 h and released about 99.91 ± 1.84% of drug in 12 h, and then followed non-Fickian diffusion release mechanism with n value of 0.635. The RBF12 tablets with BaSO4 remained in stomach for 5.13 ± 0.64 h (n=3) in radiological studies. The formulation, RBF12 exhibited maximum bioadhesive strength (1.346 ± 0.110 N) than other formulations. The bioavailability studies were carried out for the optimized formulation (RBF12) and compared with that of reference IR tablets “Rebagen” in nine healthy human volunteers. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0–∞, and MRT of RBF12 and IR tablets. The increase in relative bioavailability of RBF12 was 1.7-fold when compared to reference IR tablets. The increased relative oral bioavailability may be due to the floating-bioadhesive mechanism of dosage form, which is desirable for drugs absorbed from the upper part of gastrointestinal tract.