Sustained Release Drug Delivery System Research Articles

Dutasteride nanoemulsion preparation to inhibit 5-alpha-hair follicle reductase enzymes in the hair follicle; an ex vivo study.

Alopecia is a treatable disorder that usually occurs due to high levels of 5-alpha dihydrotestosterone in hair follicles. To enhance the storage capacity of hair follicles and alleviate the inherent characteristics of dutasteride, 5-alphareductaseinhibitor, a prolonged-release nanocarrier was synthesised, and its influence on rat abdomen's skin was investigated. Results showed the lower ratio of S/Co (higher ethanol concentration) increased the hydrodynamic nanocarriers' particle size due to thermodynamic disturbance and Ostwald ripening. In contrast, an increase in surfactant through a decrease in interfacial tension resulted in smaller nanocarriers of 32.4nm. Moreover, an increase in viscosity had an inverse correlation with the nanoemulsions' particle size. Nanocarriers containing ethanol showed less entrapment efficacy, perhaps due to the rapid dissolution of dutasteride into ethanol during nanoemulsification, while, based on Stokes' equation, the addition of ethanol resulted in smaller particle size and stability of the system. Skin permeation analysis using Franz diffusion cells showed nanocarriers could pass through the skin and release dutasteride for 6days. In conclusion, the optimum concentration of ingredients is decisive in guaranteeing the ideal particle size, stability, and skin permeation of nanocarriers. The Present dutasteride nanocarrier would promise a prolonged and sustained-release drug delivery system for Alopecia therapy.

Injectable rapidly dissolving needle-type gelatin implant capable of delivering high concentrations of H2O2 through intratumoral injection

Intratumoral injections can reduce systemic absorption and deliver large amounts of drugs to the tumor, thereby reducing side effects and exhibiting high therapeutic efficacy. Therefore, a variety of drug delivery systems, such as hydrogels, fine particles, and nanoparticles, have been studied. Although the sustained-release drug delivery system can effectively reduce systemic absorption due to the slow release of the drug from the site of intratumoral injection, it lacks the ability to deliver high concentrations of drugs to the tumor. In particular, the larger the tumor size, the lower the efficacy of the treatment. To address this problem, this study focused on the tumor structure. Owing to the three-dimensional structure of the dense tumor microenvironment (TME) and abnormal blood vessels, drugs administered directly into the tumor act as if they were encapsulated in a hydrogel. To evaluate whether the three-dimensional structure of the tumor affects the intratumoral distribution and systemic absorption of drugs, needle-type starch implants (GOD-NS implants) and needle-type gelatin implants (GOD-NG implants) containing glucose oxidase (GOD), a protein that exhibits anti-cancer effects through hydrogen peroxide (H2O2) generation, were prepared. Both GOD-NS and GOD-NG implants can be easily injected into tumors. GOD-NS implants released GOD slowly, whereas GOD-NG implants released most of the GOD within 1 h. When a GOD-NG implant that rapidly released GOD was also injected, a high concentration of GOD was maintained in the tumor for a long time as it was trapped in the three-dimensional structure of the tumor. This study demonstrated that intratumoral injection of a rapidly drug-releasing gelatin needle may be a novel drug delivery system capable of long-term retention of high drug concentrations in tumors, as the three-dimensional structure of the tumor affects drug delivery.

Preparation and Evaluation of a Sulfadimethoxine‐Conjugated Hydrogel Based on N‐isopropylacrylamide as a Sustained Release Drug Delivery System

AbstractThe burst release of drugs limited the development of the thermo‐responsive hydrogels based on poly N‐isopropylacrylamide (NIPAAm) for application in drug delivery systems. To overcome this problem, the drug sulfadimethoxine (SDMO) was conjugated via amide bond to the PNIPAAm hydrogel instead of loaded into the system. Therefore, SDMO was modified using maleic anhydride to get N‐maleyl sulfadimethoxine (NMSDMO) and then utilized that to synthesize the sulfadimethoxine‐conjugated PNIPAAm hydrogel (P[NIPAAm‐co‐NMSDMO]). The resultant monomer was then grafted into the hydrogel network at different weight percentage through radical polymerization. The NMSDMO monomer and the P[NIPAAm‐co‐NMSDMO] hydrogels were fully investigated. The in vitro drug released displayed sustained release in pH 5 and 7.4 for 24 h. Hydrolysis of the amide bond causes the release rate and total amount of drug to be greatest at pH 5, as compared to pH 7.4. As a result, the P[NIPAAm‐co‐NMSDMO] hydrogel was an effective sustained drug delivery system.

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.

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.

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.

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.

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.

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.

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.

A pH-responsive, biocompatible, and non-toxic citric acid cross-linked polysaccharide-based hydrogel from Salvia spinosa L. offering zero-order drug release

Salvia spinosa seeds hydrogel (SSH) was chemically cross-linked with four different concentrations of citric acid (CA), i.e., 1.25%, 2.5%, 5.0%, and 10.0%. The fabrication of CA cross-linked SSH (CA-cl-SSH) was confirmed through Fourier transform infrared spectroscopic analyses. The CA-cl-SSH appeared thermally as stable as SSH. The CA-cl-SSH was found pH-sensitive and exhibited maximum swelling in deionized water (DW) as compared to the buffers of pH 1.2, 6.8, and 7.4 following the order pH 1.2 < pH 6.8 < pH 7.4 < DW. Stimuli-responsive swelling and deswelling (on-off switching) behavior of CA-cl-SSH (2.5% CA) was found reversible at pH 7.4 and 1.2, in DW and normal saline, and DW and ethanol. CA-cl-SSH sustained the release of aceclofenac following the zero-order kinetics and non-Fickian diffusion mechanism. The in vivo radiographic images revealed the presence of CA-cl–SSH–based tablet formulation in GIT for 9 h. Hemocompatibility studies confirmed the non-thrombogenic and non-hemolytic potential of CA-cl-SSH. Acute oral toxicity study presented its safety profile owing to the absence of any mortality and toxic effects. Therefore, it can be concluded that CA-cl-SSH is a novel stimuli-responsive, biocompatible, and non-toxic polysaccharide-based biomaterial having the potential for the development of sustained-release drug delivery system following zero-order kinetics.

Development of an amorphous based sustained release system for apremilast a selective phosphodiesterase 4 (PDE4) inhibitor

Apremilast is a selective PDE4 inhibitor and has been approved for several inflammatory disorders. It is classified as a BCS-IV drug and has 7 polymorphic forms. In this research we report the development of an ASD based sustained-release (SR) drug delivery system. A simplified material sparing ASD formulation approach was employed to identify ideal carrier polymers for optimum drug loadings. HPMCAS-M at 20% and Copovidone at 40% drug loadings were selected as the lead formulations. A stable single-phase amorphous system of apremilast via spray drying was created and fully characterized by mDSC, XRPD, DMA, micro-dissolution, dissolution, and accelerated stability analysis. Micro-dissolution study of ASD confirmed attainment and maintenance of supersaturated state over 3 h. ASD showed 8-fold higher solubility relative to its crystalline counterpart. Novel monolithic and bilayer SR HPMC tablet matrices containing 30 mg or 60 mg of ASD system were manufactured. Tablets during dissolution exhibited gradual swelling, erosion, and disentanglement over 15–20-hours with over 90% drug released. The designed SR amorphous based matrix system showed ability to increase apremilast solubility, dissolution rate, and inhibit recrystallization or polymorphic interconversion by stabilizing its amorphous form. This new development may allow for once-daily drug administration and improve both bioavailability and patient compliance.

Targeting Ocular Drug Delivery: An Examination of Local Anatomy and Current Approaches.

Ocular drug delivery remains the focus of much modern research. Primary routes of administration include the surface, the intravitreal space, the subretinal space, and the subconjunctival space, each with its own series of unique challenges, limitations, and advantages. Each of these approaches requires careful consideration of the local anatomy, physical barriers, and key cells as well as the interface between the anatomy and the drug or drug system being delivered. While least invasive, the topical route poses a challenge with the many physical barriers that prevent drug penetration into the eye; while injection into the intravitreal, subretinal, and subconjunctival spaces are direct and targeted but limited due to the many internal clearance mechanisms and potential for damage to the eye. Polymeric-based, sustained-release drug delivery systems have been identified as a potential solution to many of these challenges; however, the design and successful implementation of a sustained-release system that is well-tolerated, bioactive, biocompatible, and degradable remains, in many cases, only in the early stages. The drugs and biomaterials in question also require special attention as small chemical changes could result in vastly different outcomes. This paper explores the anatomy and key cells of these four primary drug delivery routes as well as the interface between drug and drug delivery systems and the anatomy, reviewing the recent developments and current state of research in each area. Finally, this paper also examines the frequently used drugs and biomaterials found in ocular drug delivery and summarizes the primary interactions observed.