Sustained Release Drug Delivery Research Articles

Formulation and In- Vitro Evaluation of Baclofen Gastroretentive Microballoons for Sustained Drug Delivery

Abstract: A sustained release drug delivery system for baclofen was designed to increase its residence time in the stomach without establishing contact with the mucosa. This was made possible through the preparation of microballoons by emulsion solvent diffusion-evaporation technique. The prepared microballoons were characterized for physical characteristics such as particle size, particle shape and surface morphology by scanning electron microscopy. Further, percentage yield determination, drug entrapment efficiency, in vitro buoyancy test, micromeritic investigations and in vitro drug release studies were carried out. The obtained microspheres were free flowing, spherical and displayed a particle size ranging from 50.15 to 67.0µm suitable for oral delivery. The drug entrapped in the hollow microspheres increased with the increase in eudragit RSPO content. Scanning electron microscopy and particle size analysis revealed differences in the formulations in respect to their appearance and size distribution. The FTIR spectroscopy technique and DSC were carried out to rule out drug – excipients interactions. From the results obtained, it was concluded that there was no interaction between drug and the excipients. The formulation containing Baclofen:Eudragit RSPO (1:3 and 1:4) exhibited higher percentage values for buoyancy time. The drug release was found to follow Higuchi kinetics with non-fickian diffusion mechanism, from all the four batches. These preliminary results indicate that baclofen loaded microballoons could be effective in sustaining drug release for prolonged periods of time

Polyester-Polydopamine Copolymers for Intravitreal Drug Delivery: Role of Polydopamine Drug-Binding Properties in Extending Drug Release.

This work reports on a novel polyester copolymer containing poly(dopamine), a synthetic analogue of natural melanin, evaluated in a sustained-release drug delivery system for ocular intravitreal administration of drugs. More specifically, a graft copolymer of poly(ε-caprolactone)-graft-poly(dopamine) (PCL-g-PDA) has been synthesized and was shown to further extend the drug release benefits of state-of-the-art biodegradable intravitreal implants composed of poly(lactide) and poly(lactide-co-glycolide). The innovative biomaterial combines the documented drug-binding properties of melanin naturally present in the eye, with the established ocular tolerability and biodegradation of polyester implants. The PCL-g-PDA copolymer was obtained by a two-step modification of PCL with a final PDA content of around 2-3 wt % and was fully characterized by size exclusion chromatography, NMR, and diffusion ordered NMR spectroscopy. The thermoplastic nature of PCL-g-PDA allowed its simple processing by hot-melt compression molding to prepare small implants. The properties of unmodified PCL and PCL-g-PDA implants were studied and compared in terms of thermal properties (differential scanning calorimetry), thermal stability (thermogravimetry analysis), degradability, and in vitro cytotoxicity. PCL and PCL-g-PDA implants exhibited similar degradation properties in vitro and were both stable under physiological conditions over 110 days. Likewise, both materials were non-cytotoxic toward L929 and ARPE-19 cells. The drug loading and in vitro release properties of the new materials were investigated with dexamethasone (DEX) and ciprofloxacin hydrochloride (CIP) as representative drugs featuring low and high melanin-binding affinities, respectively. In comparison to unmodified PCL, PCL-g-PDA implants showed a significant extension of drug release, most likely because of specific drug-catechol interaction with the PDA moieties of the copolymer. The present study confirms the advantages of designing PDA-containing polyesters as a class of biodegradable and biocompatible thermoplastics that can modulate and remarkably extend the drug release kinetics thanks to their unique drug-binding properties, especially, but not limited to, for ocular applications.

EVALUATION OF DIACEREIN MICROSPHERE MANUFACTURED BY FLUID BED BOTTOM SPRAY COATING TECHNIQUE AS SUSTAINED RELEASE DRUG DELIVERY FORM

Diacerein (DCN), an anti- inflammatory, anti-osteoarthritic drug having short-acting properties was formulated as microsphere following fluid bed bottom spray coating technique for sustained release drug delivery, where HPMC (6cps) and ethyl cellulose (N7) were used as coating polymers. Assay of DCN microsphere was done following HPLC method. Drug content in microsphere was found to be 147 mg g-1. Drug entrapment efficiency was calculated as 61%. SEM study of microsphere showed that microsphere was spherical in shape and porous in structure. Particle size, size distribution, zeta potential and poly disparity index were studied by dynamic light scattering method. particle size range was found between 396-615nm, zeta potential 10.8-19.6mv and PDI 0.65. In vitro drug release rate from microsphere was studied in different buffers like phosphate (pH 6.8), citrate (pH 6.0) and acidic medium (0.1N HCL). DCN microsphere released about 97% of its drug content in 20 h in phosphate buffer, 57.8% of its drug content in citrate buffer in 20 h and negligible drug release was found in acidic medium. On the contrary, market preparation of diacerein 50 mg capsule (Orcerin, Macleod’s) released 80% of its drug content in 1 h in phosphate and citrate buffer. Pharmacokinetic study of DCN microsphere vis a vis DCN capsule market preparation in plasma level of rabbit showed as Cmax4.02/3.97 mcg ,Tmax4h/ 2.67h, AUC0-t 21.26/17.80 mcg h mL-1, AUC 0-∞ 21.35/19.38 mcg h mL-1, T1/2 1.98/ 2.30 h and Kel 0.35/0.31. Study as mentioned above showed that DCN microsphere manufactured by fluid bed bottom spray coating technique using HPMC (6cps) and ethyl cellulose (N7) as coating polymers exhibited sustained release drug delivery. So it is a useful method for manufacture of sustained release dosage form.

Formulation Development, Evaluation and Statistical Optimization of the Release Rate of Oral Sustained Release Matrix Tablet of Aceclofena

Aim: This work aimed to develop a sustained released hydrophilic matrix tablet of Aceclofenac for better therapeutic action. 
 Background: Conventional dosage form didn't provide the desired level of drug release. Even many-marketed sustained-release tablets didn't always meet the satisfactory level of drug release. It was a challenging job for pharmaceutical scientists to develop a well-sustained release formulation. Keeping this perspective in mind a robust sustained release formulation was designed, developed and optimized with nontoxic, inert viscoelastic, semisynthetic polymers which will be accepted worldwide.
 Objective: The objective of this research was to develop an Aceclofenac sustained released matrix tablet, which will deliver the desired level of drug release.
 Method: Aceclofenac sustained released tablet was prepared with Methocel K-100M Premium (Hydroxypropyl Methylcellulose) and Unigel 270 (Pregelatinized starch). These two excipients were selected as independent formulation variables with three separate levels (high, intermediate and low). Nine batches of hydrophilic matrix tablets of Aceclofenac were prepared according to the 32 Factorial Design with an average weight of 365 mg/tablet. Each prepared batch of tablets was then evaluated for drug content, physical parameters and drug release. Mathematical models were then generated using Analysis of Variance employing Design-Expert Software version 8.0.7.1 for % cumulative release at T1 hr, T4 hr and T7 hr. FTIR spectroscopy was carried out to evaluate drug-excipients interaction after formulation.
 Results: Design-Expert Software after analyzing the release data of prepared 9 batches provides an optimized composition of formulation. The optimized batch showed desirable results for cumulative % release (CPR)T1hr, CPR T4hr and CPR T7hr are 35.61, 52.16 and 61.98 respectively. 
 Conclusion: Application of statistical experimental design, the physicochemical studies and the in vitro-release study, the mathematically predicted formulation and its manufacturing and validation of aceclofenac sustained-release tablets showed great advancement from the trial-and-error method of development of sustained-release drug delivery systems.

Lyotropic liquid crystals for parenteral drug delivery

The necessity for long-term treatments of chronic diseases has encouraged the development of novel long-acting parenteral formulations intending to improve drug pharmacokinetics and therapeutic efficacy. Lately, one of the novel approaches has been developed based on lipid-based liquid crystals. The lyotropic liquid crystal (LLC) systems consist of amphiphilic molecules and are formed in presence of solvents with the most common types being cubic, hexagonal and lamellar mesophases. LC injectables have been recently developed based on polar lipids that spontaneously form liquid crystal nanoparticles in aqueous tissue environments to create the in-situ long-acting sustained-release depot to provide treatment efficacy over extended periods. In this manuscript, we have consolidated and summarized the various type of liquid crystals, recent formulation advancements, analytical evaluation, and therapeutic application of lyotropic liquid crystals in the field of parenteral sustained release drug delivery.

Sustained Release Matrix Technology for Cefixime- A Review

Sustained release drug delivery system is designed to sustain the release of the drug dosage forms at a predetermined rate. Sustained release formulation maintains uniform drug level in therapeutic window, improved efficacy of drug by localization at the site of action with better patient compliance, reducing the dose required, providing uniform drug delivery. The sustained release formulations minimize the frequency of drug administration and do not interfere with the therapeutic action of the drug. The use of sustained release matrix technology for antibiotics is effective in preventing the resistant of antibiotics in body on irrational use. Drug release through matrix SRDDS is determined by Polymer swelling, Water penetration, Drug dissolution, diffusion, Matrix erosion. The present article contains brief review on various formulation approaches for Sustained release drug delivery system, advantages, selection criteria for matrix SRDDS and use of cefixime trihydrate in formulating matrix SRDDS.

Dual sustained-release PTMC/PCL porous microspheres for lipid-soluble drugs

It is still a considerable research challenge to design biodegradable drug delivery systems that efficiently transport lipid-soluble drugs with controlled release. In the present study, a microsphere delivery system, γ-cyclodextrin (γ-CD)/glutathione (GSH)-atorvastatin (AT) fibrous nanoparticles (γ-CD/GSH-AT FNs) loaded polytrimethylene carbonate (PTMC)/polycaprolactone (PCL) microspheres (PTMC/PCL/γ-CD/GSH-AT MPs), was constructed through an exquisite method. The results show that a large number of γ-CD/GSH-AT FNs can be encapsulated during the formation of microspheres and released in a controllable manner. Notably, the high dispersibility and drug loading of FNs can load with lipid-soluble drugs and protect the drugs from the solvent during microsphere preparation. FNs and MPs can achieve dual release. First, with the degradation of the microspheres, the encapsulated FNs were gradually released into the local microenvironment. Subsequently, the FNs began to dissolve and release the loaded AT over a period of more than 3 days. Therefore, the dual sustained-release drug delivery system can maintain the blood drug concentration for a longer time and reduce the number of administrations and the side effects of the drug. This study provides new ideas for the on-demand manufacture of controllable degradable drug delivery platforms to treat diseases.

Impact of Carboxymethylation of Albizia procera Gum on Rheological Changes and Drug Release from Matrix Tablets

The use of carbohydrate polymers in pharmaceutical formulations as drug delivery carriers has gained significant interest from many perspectives. As an exudate of the Albizia tree, Albizia procera (Mimosaceae), a carbohydrate polymer, is used as an excipient to develop sustained-release drug delivery systems, owing to its biocompatibility and biodegradability. This study was conducted to investigate the influence of carboxymethylation of A. procera gum on rheological properties and drug release from the matrix tablet formulations. The study also revealed the comparative characterization of the native form of A. procera (NAP) as well as the carboxymethylated A. procera (CMAP). The rheological assessments of both polymers under different pH divulged the flow behavior, linear viscoelasticity (LVE), structural deformation, and gel network formation. The drug release from NAP and CMAP matrices of various formulations were evaluated and established correlations with rheology.

Sustainable Drug Release Using Nanoparticle Encapsulated Microneedles.

Microneedle (MN) is a minimally invasive drug delivery method that is directly inserted into the skin without pain to improve the efficiency of transdermal administration and is a drug delivery system used to treat various diseases. Furthermore, nanoparticle (NP)-based drug delivery methods suggest therapeutic strategies to improve drug solubility and increase drug delivery efficiency. Therefore, the drug delivery system in which NPs and MNs are integrated is a promising alternative to the existing delivery methods of poorly soluble and hydrophobic drugs and nucleic acid therapeutics. This system can increase the solubility of drugs and biocompatibility in the body and improve the therapeutic efficacy with sustained drug release. In this review, we investigated recent studies of NPs designed for drug delivery, sustained-release drug delivery MNs based on these NPs, and the applications for clinical treatments.

Research on the Construction of Bispecific-Targeted Sustained-Release Drug-Delivery Microspheres and Their Function in Treatment of Hepatocellular Carcinoma.

Lenvatinib (LEN) is approved as one of the commonly used drugs in the treatment of hepatocellular carcinoma (HCC). It is recognized to be a novel therapeutic choice for the direct and targeted delivery of effective drugs to HCC tumor sites. The key to the proposed method lies in the requirement for efficient targeted drug delivery carriers with targeting performance to deliver effective drugs directly and safely to tumor lesions. Methods: Here, magnetic liposomes (MLs) were modified by phosphatidylinositol proteoglycan 3 (GPC3) and epithelial cell adhesion molecules (EpCAMs). Subsequently, bispecific-targeted sustained-release drug-loaded microspheres containing LEN (GPC3/EpCAM-LEN-MLs) were constructed. In addition, both cytotoxicity and magnetic resonance imaging (MRI) analyses were performed to establish a mouse model and further perform corresponding performance assessments. Results: The corresponding results showed that GPC3/EpCAM-LEN-MLs were spherical-shaped and evenly dispersed. The encapsulation and drug-loading efficiencies were 91.08% ± 1.83% and 8.22% ± 1.24%, respectively. Meanwhile, GPC3/EpCAM-LEN-MLs showed a high inhibition rate on the proliferation of HCC cells and significantly increased their apoptosis. Furthermore, MRI revealed that the system possessed the function of tracking and localizing tumor cells, and animal experiments verified that it could exert the function of disease diagnosis. Conclusions: Our experiments successfully constructed a safe and efficient bispecific-targeted sustained-release drug delivery system for HCC tumor cells. It provides a useful diagnostic and therapeutic scheme for the clinical diagnosis and targeted therapy of HCC. Moreover, it can be used as a potential tumor-specific MRI contrast agent for the localization and diagnosis of malignant tumors.

Robust gelatin hydrogels for local sustained release of bupivacaine following spinal surgery

Adequate treatment of pain arising from spinal surgery is a major clinical challenge. Opioids are the mainstay of current treatment methods, but the frequency and severity of their side effects display a clear need for opioid-free analgesia. Local anesthetics have been encapsulated into sustained-release drug delivery systems to provide postoperative pain relief. However, these formulations are limited by rapid diffusion out of the surgical site. To overcome this limitation, we synthesized ring-shaped hydrogels incorporating bupivacaine, designed to be co-implanted with pedicle screws during spinal surgery. Hydrogels were prepared by riboflavin-mediated crosslinking of gelatin functionalized with tyramine moieties. Additionally, oxidized β-cyclodextrin was introduced into the hydrogel formulation to form dynamic bonds with tyramine functionalities, which enables self-healing behavior and resistance to shear. Feasibility of hydrogel implantation combined with pedicle screws was qualitatively assessed in cadaveric sheep as a model for instrumented spinal surgery. The in-situ crystallization of bupivacaine within the hydrogel matrix provided a moderate burst decrease and sustained release that exceeded 72 hours in vitro. The use of bupivacaine crystals decreased drug-induced cytotoxicity in vitro compared to bupivacaine HCl. Thus, the presented robust hydrogel formulation provides promising properties to enable the stationary release of non-opioid analgesics following spinal surgery. Statement of significanceCurrently, postoperative pain following spinal surgery is mainly treated with opioids. However, the use of opioids is associated with several side effects including addiction. Here we developed robust and cytocompatible gelatin hydrogels, prepared via riboflavin-mediated photocrosslinking, that can withstand orthopedic implantation. The implantability was confirmed in cadaveric instrumented spinal surgery. Further, hydrogels were loaded with bupivacaine crystals to provide sustained release beyond 72 hours in vitro. The use of crystallized bupivacaine decreased cytotoxicity compared to bupivacaine HCl. The present formulation can aid in enabling opioid-free analgesia following instrumented spinal surgery.

Metal Complexation of Arabinoxylan Engenders a Smart Material Offering pH, Solvents, and Salt Responsive On-Off Swelling with the Potential for Sustained Drug Delivery.

The present study aimed to develop a stable interconnected matrix as a sustained release drug delivery material. Arabinoxylan (AX) was extracted from ispaghula husk and then crosslinked with different concentrations, i.e., 0.5, 1.0, and 1.5 g of CaCl2 per 0.25 g of AX. The crosslinking was confirmed through Fourier transform infrared spectroscopy. The swelling capacity of crosslinked AX (CL-AX) was evaluated against buffer solutions of pH 1.2, 6.8, 7.4, and water. The swelling capacity increased from pH 1.2 to pH 7.4 and followed the second order swelling kinetics. The swelling study also revealed that CL-AX with 1.0 g CaCl2 showed maximum swelling capacity. The swelling–deswelling (on–off switching) behavior of CL-AX was evaluated in water–ethanol, water–0.9% NaCl solution, and buffer solutions of pH 7.4–1.2 and showed responsive swelling–deswelling behavior. Scanning electron microscopy revealed a highly porous nature of CL-AX with a mesh of thin fibrous networking. Hemocompatibility studies of CL-AX revealed its non-thrombogenic and nonhemolytic attributes. The CL-AX matrix tablet prolonged the release of enalapril maleate for 24 h, and the drug release followed the zero order kinetics and super case-II transport mechanism. Therefore, CL-AX can be recognized as a stimuli responsive and hemocompatible biomaterial with sustained drug release potential.

Formulation and evaluation of sustained release tablets of propranolol hydrochloride

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.

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

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.

An updated review on microspheres: a suitable drug carrier in sustained release drug delivery

With advances in biotechnology, genomics, and combinatorial chemistry, a wide variety of new, more potent and specific therapeutics are being created. Because of common problems such as low solubility, high potency, and/or poor stability of many of these new drugs, the means of drug delivery can impact efficacy and potential for commercialization as much as the nature of the drug itself. Thus, there is a corresponding need for safer and more effective methods and devices for drug delivery. Microspheres having particle size in range between 0.1-200 µm, can be delivered by several routes like oral, parentral, nasal, ophthalmic, transdermal, colonal etc. In future by combining various new strategies, microspheres will find a central place in novel drug delivery, particularly in diseased cell sorting, genetic materials, safe, targeting and effective drug delivery.

Design, synthesis, and evaluation of a novel series of mono-indolylbenzoquinones derivatives for the potential treatment of breast cancer

Breast cancer is one of the most common cancers in the world, and pro-apototic drugs activating the apoptotic pathway are a strategy for anticancer therapy. To explore new antineoplastic agents, a series of novel mono-indolylbenzoquinone derivatives have been designed and synthesized. Compared with the lead bis-indolylbenzoquinones, most of the novel mono-indolylbenzoquinone derivatives have significantly increased their activity against A549, HeLa, and especially, MDA-MB-231 cell lines. Among them, 10d has the lowest IC50 value of 70 nM on MDA-MB-231 cells. Moreover, its oral toxicity is extremely low with an LD50 value of 374 mg/kg and no obvious liver and kidney damage to mice. 10d down-regulated Bcl-2, up-regulated Bax, and increased the release of cytochrome C, caspase3 and 9. 10d also up-regulated the expression of p53, catalase, and HTRA2/Omi. Therefore, 10d may exert its anticancer activity by activating apoptotic pathway and p53 expression. In vivo, 10d suppressed breast cancer 4T1 tumor growth with 36% inhibition ratio of tumor by intraperitoneal injection in mice. Furthermore, a cross-linked cyanoacrylate (CA)-based local sustained-release drug delivery systems (LSRDDSs) improved 10d anticancer activity to 49.8% inhibition of tumor growth. Taken together, 10d could be a promising drug candidate for clinical development to treat metastatic breast cancer.

Pulsatile Drug Delivery System (PDDS): A Cronotherapeutic Approach for Optimum Therapy

Now a day’s PDDS are gaining more attraction and importance especially for the disease follow circadian rhythms. Some chronic disease like rheumatoid arthritis, asthma, hypercholesterolemia, hyper acidity and cardio vascular diseases where peak symptoms tends to follow a 24 hour cycle called circadian rhythms. Optimum therapy of these diseases demands a drug delivery system where Cmax of the drug achieve exactly at the time of peak of the disease. This is only possible by chronotherapeutic approach i.e. pulsatile drug delivery system. This delivery system not only releases the right amount of drug at the right time but also overcome the other challenges like drug tolerance and over dose associated with traditional sustained or extended release drug delivery system. Drugs under goes extensive first pass metabolism, degradation in gastric acid medium, having biological tolerance and targeted to distal parts of GIT are suitable candidates for PDDS. It has many advantages like pre-programmed delayed-release, multiple dosing option, reduce drug loss, less drug interaction and improve patient compliance etc There are various technologies of PDDS like C O D A S ® ,O R O S ® , DIFFUCAPS ®,3D Printing, PULSINCAPTM are already available in the market. The current work is focused on the requirements, advantages, disadvantages and a review on various drugs and polymers used to develop PDDS in current & past decades. The study revealed that, PDDS has a tremendous scope and can play a vital role in the optimum treatment of many chronic diseases which follows circadian rhythm.

Chitosan-coated contact lens-based ophthalmic drug delivery system to manage Acanthamoeba keratitis: a preliminary hypothesis

Background: Acanthamoeba species can cause devastating contact lens (CL)-related microbial keratitis. Its culture is less sensitive, and little evidence is available for the safety or efficacy profile of medications. Therefore, early diagnosis and optimal treatment remain difficult. The aim of this study was to present the hypothesis that a novel chitosan-coated CL-based ophthalmic drug delivery system has therapeutic and prophylactic effects on acanthamoeba keratitis.
 Hypothesis: CL-based drug delivery is a popular sustained-release drug delivery that extends the drug release time, thus increasing its bioavailability and treatment efficacy. Chitosan, a derivative of chitin, has antioxidant and broad-spectrum antimicrobial properties against fungi, yeasts, and bacteria. It acts against microbial cells; however, whether its mechanism of action is microbiostatic or microbicidal remains unknown. It exhibits wound healing and film-forming properties. Chitosan composite films permit high transmittance of visible light, making it transparent and therefore desirable for the development of CLs. Chitosan/Ag/ZnO blend films exhibit antimicrobial activities. Further, soft CLs coated with chitosan, sodium hyaluronate, polylysine hydrobromide, and sodium alginate show drug delivery properties and reduced bacterial growth. Recently, concentration-dependent anti-amoebic activities of chitosan and nano-chitosan against the trophozoite and cystic forms of Acanthamoeba have been reported. Based on the existing evidence, we hypothesized that a chitosan-coated CL-based ophthalmic drug delivery system could have therapeutic and prophylactic effects on acanthamoeba keratitis or subsequent endophthalmitis.
 Conclusions: CLs or intraocular implants with chitosan-based nanocoatings alone or in combination with routine treatment may be preventive or therapeutic for acanthamoeba keratitis or endophthalmitis. Experimental studies and further clinical trials are required to explore the efficacy and safety profile. Moreover, randomized controlled trials in healthy eyes with soft or hard CLs or orthokeratology lenses for refractive error correction may shed light on the prophylactic effect of this novel drug delivery system. Other forms of ophthalmic drug delivery systems using chitosan-based nanocoatings should be studied additionally.

Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage

Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments are not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for OA may be an attractive strategy to prevent rapid drug clearance and improve the half-life of a drug at the joint cavity. Such delivery systems will improve the therapeutic effects of anti-inflammatory effects in the joint cavity. Whereas, for disease-modifying OA drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), the cartilage-permeable DDSs are required to maximize their efficacy. This review provides an overview of joint structure in healthy and pathological conditions, introduces the advances of the sustained-release DDSs and the permeable DDSs, and discusses the rational design of the permeable DDSs for OA treatment. We hope that the ideas generated in this review will promote the development of effective OA drugs in the future.

DEVELOPMENT AND EVALUATION OF RAFT FORMING GASTRO RETENTIVE FLOATING DRUG DELIVERY SYSTEM OF NIZATIDINE BY DESIGN OF EXPERIMENT

Objective: The current research involves the formulation of a sustained-release gastro-retentive drug delivery system of nizatidine. Methods: Using 33 Box-Behnken designs, about 17 experiments were performed and evaluated for various parameters like physical appearance, pH, in vitro gelling study, in vitro buoyancy study, measurement of viscosity, density measurement, gel strength, raft resilience, drug content, acid neutralization capacity, in vitro dissolution, release kinetics and stability studies. Results: All the formulations exhibited good viscosity, density less than gastric fluid, gelling capacity retained, and buoyant for 12 h. Drug content ranges from 97.98 to 99.34 %, with a long neutralization period. The buoyancy lag time was found to be in the range of 15.34 to 26.12 sec and the % drug release at 12 h was between range from 85.67 to 99.45, with the highest release exhibited by F3. All formulations displayed zero order in vitro drug release>10 h with exceptional buoyancy properties. F3 was the optimized formulation and further subjected to FTIR and DSC study, concluding that compatibility of nizatidine with excipients in the formulation blend. Stability studies show no significant changes. Conclusion: Results indicate that gastric-floating formulations of nizatidine have the prospective for superior gastric residence time and sustained drug release.