Sustained release ocular drug delivery systems for glaucoma therapy

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

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.

Natural polymer-based plant polysaccharides and proteins have been most widely explored as an adjuvant in the dosage form formulation. Here we design a novel gastro-retentive floating tablet, based on a polysaccharide material from Flaxseed (Linum usitatissimum L.) for Domperidone. After oral administration; Domperidone showed good solubility in acidic pH but significantly reduced solubility in alkaline medium. So that to increase the absorption and bioavailability of Domperidone, it is necessary to increase the retention time in the upper part of the Gastrointestinal tract (GIT) by developing a floating sustained drug delivery system. The directly compressible floating tablets of domperidone were formulated using varying amount of hydroxypropyl methylcellulose K 100 M (HPMC K100 M), Carbopol 934 and Flaxseed mucilage. Hardness, friability, weight variation, thickness, disintegration time of tablet formulations were within acceptable limits. The overall results explained that the optimized formulation F5 prepared by the exact ratio of Flaxseed mucilage, HPMC K100 M, Carbopol, could be more efficient on floating and sustained release of Domperidone in the upper part of GIT as compared to the tablets prepared by using HPMC K100 M and Carbopol 934 only. These findings indicated that Flaxseed can be used to develop novel gastro-retentive sustained release drug delivery system with the double advantage of sustained drug release at the upper part of GIT.

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.

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.

RSM optimized chitosan based composite hydrogel for sustained drug delivery applications

Introduction Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Area Covered This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care. Expert Opinion Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.

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.

Liposomes have proven to be versatile carriers for the delivery of drugs. These carriers are biocompatible, since they are generally made from lipids commonly found in biologic systems and are biodegradable by the usual metabolic pathways. A sustained drug delivery system is useful when the efficacy of drugs is limited by the inability to maintain therapeutic concentrations. Furthermore, a depot delivery system can offer important advantages in the clinic, such as significantly reducing dose frequency and providing efficacy without toxicity. Because of their small size (<5μ.m), conventional liposomes (unilamellar and multilamellar) are limited in their ability to provide depot delivery of drugs when administered subcutaneously or intramuscularly. The small size of these liposomes results in relatively fast clearance from the injection site and a short duration of delivery, typically 1–4 days. Multivesicular liposomes (MVLs) are distinct from conventional liposomes in composition, structure, and size and are the only class of commercial liposomes that have demonstrated depot delivery of both small molecule and protein/peptide drugs. These MVLs are characterized by the presence of a continuous bilayer membrane, with numerous internal aqueous compartments that are contiguous and separated by bilayer septums. As a result of their larger size (median diameter typically 10–30μ.m), these MVLs are not rapidly cleared by tissue macrophages and can act as a drug depot providing slow release of drugs delivered through different routes of administration. Moreover, the biocompatibility and biodegradability of the MVL lipid matrix allows for the sustained delivery of drugs to sensitive areas. The unique architecture of MVLs provides high drug loading of water-soluble drugs, reasonable stability during storage, and control over the drug-release rate. Furthermore, the lipid composition of MVLs can be altered to deliver therapeutics over periods ranging from a few days to a month, in order to meet specific therapeutic needs. The capability of altering the rate of drug release from MVLs by varying the lipid composition provides a great deal of versatility for controlled delivery of a wide variety of therapeutics. This article reviews depot delivery with conventional liposomes, demonstrates through several examples the sustained depot delivery of small and macromolecular drugs using MVLs, and summarizes some novel delivery systems that combine liposomes with polymeric matrices and have the potential to expand the platform of liposomal depot delivery.

Fluocinolone acetonide sustained drug delivery device to treat severe uveitis

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

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

The present study aimed to develop and evaluate a diclofenac sodium-loaded nanostructured lipid carrier (NLC) gel for enhanced topical management of arthritis. Diclofenac sodium-loaded NLCs were prepared using the solvent injection technique and incorporated into Carbopol 940 gel to improve topical applicability and sustained drug delivery. The optimized NLC gel was characterized for physicochemical properties, in vitro drug release, ex vivo skin permeation and retention, and In Vivo anti-arthritic efficacy. The optimized formulation exhibited acceptable pH, viscosity, spreadability, and uniform drug content, along with sustained drug release over 12 h. Ex vivo studies using porcine skin demonstrated significantly enhanced drug permeation and skin retention for the NLC gel compared to marketed diclofenac gel and blank gel. In Vivo evaluation in Complete Freund’s Adjuvant-induced arthritic rats revealed a pronounced reduction in paw edema, arthritis score, and improvement in body weight in animals treated with diclofenac sodium NLC gel. Histopathological analysis further confirmed reduced synovial hyperplasia, inflammatory cell infiltration, cartilage erosion, and bone destruction, indicating effective suppression of arthritic pathology. Overall, the findings suggest that diclofenac sodium-loaded NLC gel offers superior topical anti-arthritic efficacy with sustained local drug delivery and reduced systemic burden, making it a promising alternative for localized arthritis therapy.

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.

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