Sustained Release Microparticles Research Articles

An in vitro model for postoperative cranial nerve dysfunction and a proposed method of rehabilitation with N-acetylcysteine microparticles.

When operating near cranial motor nerves, transient postoperative weakness of target muscles lasting weeks to months is often observed. As nerves are typically intact at a procedure's completion, paresis is hypothesized to result from a combination of neurapraxia and axonotmesis. As both neurapraxia and axonotmesis involve Schwann cell injury and require remyelination, we developed an in vitro RSC96 Schwann cell model of injury using hydrogen peroxide (H2O2) to induce oxidative stress and investigated the efficacy of candidate therapeutic agents to promote RSC96 viability. As a first step in developing a long-term local administration strategy, the most promising of these agents was incorporated into sustained-release microparticles and investigated for bioactivity using this assay. The concentration of H2O2 which reduced viability by 50% was determined to establish a standard for inducing oxidative stress in RSC96 cultures. Fresh cultures were then co-dosed with H2O2 and the potential therapeutics melatonin, N-acetylcysteine, resveratrol, and 4-aminopyridine. Schwann cell viability was evaluated and the most efficacious agent, N-acetylcysteine, was encapsulated into microparticles. Eluted samples of N-acetylcysteine from microparticles was evaluated for retained bioactivity. 100µM N-acetylcysteine improved the viability of Schwann cells dosed with H2O2. 100µM Microparticle-eluted N-acetylcysteine also enhanced Schwann cell viability. We developed a Schwann cell culture model of iatrogenic nerve injury and used this to identify N-acetylcysteine as an agent to promote recovery. N-acetylcysteine was packaged into microparticles and demonstrated promise as a locally administrable agent to reduce oxidative stress in Schwann cells.

Transdermal Drug Delivery System of Linagliptin Sustained-release Microparticle Gels: In vitro Characterization and In vivo Evaluation.

Linagliptin (LNG) exhibits poor bioavailability and numerous side effects, significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to overcome the first-pass effect and gastrointestinal reactions associated with oral formulations. The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability and mitigate side effects. Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying method and their formulation was optimized via a one-factor method. The solubility and release were investigated using the slurry method. LNG-HA microparticle gels were prepared and optimised using in vitro transdermal permeation assay. The hypoglycaemic effect of the LNG-HA microparticle gel was examined on diabetic mice. The results indicated that the LNG-HA microparticle encapsulation rate was 84.46%. Carbomer was selected as the gel matrix for the microparticle gels. Compared to the oral API, the microparticle gel formulation demonstrated a distinct biphasic release pattern. In the first 30 minutes, only 43.56% of the drug was released, followed by a gradual release. This indicates that the formulation achieved a slow-release effect from a dual reservoir system. Furthermore, pharmacodynamic studies revealed a sustained hypoglycemic effect lasting for 48 hours with the LNG microparticle gel formulation. These findings signify that the LNG microparticle gel holds significant clinical value for providing sustained release and justifies its practical application.

Development and In Vivo Evaluation of Sustained Release Microparticles Loaded with Levothyroxine for Hypothyroidism Treatment

Hypothyroidism is a chronic condition combated by a daily oral supplementation of levothyroxine. In addition to the need for frequent dosing, oral administration may result in variable absorption of the drug leading to a failure in achieving normal thyroid function. Therefore, the development of a long-acting injectable system capable of delivering the drug is necessary. This work was aimed at developing sustained release microparticles loaded with levothyroxine. The microparticles were produced through the emulsification-solvent evaporation method using 2 grades of biocompatible and biodegradable polyesters: poly(ᴅ,ʟ-lactide-co-glycolide) (PLGA) and poly(ᴅ,ʟ-lactide) (PLA). Both polymers produced microparticles with very similar sizes (1.9 µm) and zeta potential values (around -22.0 mV). However, PLA microparticles had a significantly higher drug loading (6.1% vs. 4.4%, respectively) and encapsulation efficiency (36.8%, vs. 26.1%, respectively) when compared to PLGA counterparts. While both types of microparticles displayed a biphasic release pattern in vitro, a slower rate of release was observed with PLA microparticles. Moreover, a similar biphasic release pattern was found in vivo, with an initial phase of rapid release followed by a slower phase in the subsequent 10 days. These results indicate the possibility of developing levothyroxine loaded polyester microparticles as a potential long-acting thyroid hormone replacement therapy.

Electrosprayed Poly-butyl-succinate microparticles for sustained release of Ciprofloxacin as an antimicrobial delivery system

The increasingly complex treatment of bacterial infections, and its relevance in the clinical setting, requires the development of innovative strategies to improve patients' quality of life. In this context, polymeric microparticles represents a versatile drug delivery system (DDS) capable of improving the antibiotics' efficacy in the treatments, by loading drugs while modifying their release profile. In this study we aimed to produce polymeric microparticles by electrospraying using Poly-Butyl-Succinate (PBS), a biodegradable and biocompatible polyester. This versatile and easy-to-use technique enabled the incorporation of the poorly water-soluble Ciprofloxacin (CPX) into the polymer matrix. CPX is a fluoroquinolone antibiotic, inhibiting bacterial replication and effectively treating various infections. PBS is a well-known water-insoluble polymer with tuneable chemical-physical properties, also used for tissue regeneration and wound healing applications. An ex-vivo permeation study on porcine skin, serving as a model for human skin, was performed to assess potential enhancement in drug permeation. The microparticles were characterized by means of different techniques (SEM-EDX, XRD, ATR-FTIR, DSC), and their degradation rate was tested in DPBS and human plasma. Moreover, the as-produced DDS enabled the sustained release of CPX for several days, which proved effective against S. aureus and P. aeruginosa and also against a reference group of bacteria of skin microbiota often involved in pathological processes that make wounds chronic and difficult to heal. MIC and MBC assays were conducted using different culture media. Effective antibacterial activity was observed, along with inhibition of P. aeruginosa biofilm formation at sub-MIC concentrations.

Fabrication and Characterization of Antibody-Loaded Cationic Porous PLGA Microparticles for Sustained Antibody Release.

Poly lactic-co-glycolic acid (PLGA) microparticles have been formulated to allow the sustained release of numerous drugs, including antibodies. It is well-known that antibodies are susceptible to chemical and physical stress; therefore, it is necessary to be loaded on PLGA microparticles under mild conditions. In the present study, we constructed cationic porous PLGA microparticles that could be electrostatically adsorbed with infliximab as a model antibody. Cationic porous PLGA microparticles were prepared using the double emulsion method by adding polyethyleneimine and ammonium bicarbonate. After antibody loading, surface pores closure was achieved by mild heating. The size of the optimized formulation was approximately 5 μm, exhibiting a positive charge. The loaded antibody was gradually released from the formulation over 56 days. Based on a tumor necrosis factor (TNF)-α inhibition assay, the released infliximab maintained its pharmacological activity. Collectively, we successfully loaded antibodies into PLGA microparticles while maintaining activity and demonstrating long-acting properties.

Intramuscularly Administered PLGA Microparticles for Sustained Release of Rivastigmine: In Vitro, In Vivo and Histological Evaluation

Rivastigmine is an acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibitor drug approved by the US Food and Drug Administration (FDA) for the treatment of mild to moderate dementia of Alzheimer's type. However, its first-pass metabolism and gastrointestinal side effects negatively affect the tolerability and efficacy of oral therapy. These adverse effects could be avoided with the use of a sustained -release formulation as an intramuscular (IM) administration system. The objective of this work was to develop polylactic co-glycolic acid (PLGA) microparticles for the sustained release of rivastigmine and to evaluate its stability during storage, tissue tolerance, in vitro release, and in vivo pharmacokinetics after its IM administration. The microparticles were made by the solvent evaporation emulsion method. A series of formulation parameters (the type of polymer used, the amount of polymer used, the initial amount of rivastigmine, and the volume of PVA 0.1% w/v) were studied to achieve an encapsulation efficiency (EE) and a rivastigmine load of 54.8 ± 0.9% and 3.3 ± 0.1%, respectively. The microparticles, whose size was 56.1 ± 2.8 μm, had a spherical shape and a smooth surface. FT-IR analysis showed that there is no chemical interaction between rivastigmine and the polymer. PLGA microparticles maintain rivastigmine retained and stable under normal (5 ± 3 °C) and accelerated storage (25 ± 2 °C and 60 ± 5 % RH) conditions for at least 6 months. The microparticles behaved as a sustained release system both in vitro and in vivo compared to non-encapsulated rivastigmine. The IM administration of the formulation in rats did not produce significant tissue damage. However, it is necessary to reproduce the experiments with multiple doses to rule out a negative effect in terms of tolerability in chronic treatment. To the best of our knowledge, this study is the only one that has obtained the sustained release of rivastigmine from PLGA microparticles after IM administration in an in vivo model.

In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor.

The treatment of posterior eye segment diseases through intravitreal injection requires repeated injections of an active molecule, which may be associated with serious side effects and poor patient compliance. One brilliant strategy to overcome these issues is the use of drug-loaded microparticles for sustained release, aiming at reducing the frequency of injections. Therefore, the aim of this work was to assess the safety features of poly(lactic-co-glycolic acid) (PLGA)-based, hyaluronic acid-decorated microparticles loaded with palmitoylethanolamide (PEA), citicoline (CIT), or glial-cell-derived neurotrophic factor (GDNF). Microparticles were prepared by double emulsion-solvent evaporation and fully characterized for their technological features. Microparticles possessed a satisfactory safety profile in vitro on human retinal pigment epithelial (ARPE-19) cells. Interestingly, the administration of free GDNF led to a loss of cell viability, while GDNF sustained release displayed a positive effect in that regard. In vivo results confirmed the safety profile of both empty and loaded microparticles. Overall, the outcomes suggest that the produced microparticles are promising for improving the local administration of neuroprotective molecules. Further studies will be devoted to assess the therapeutic ability of microparticles.

Hydroxyapatite Nanocoating on Calcium Peroxide Microparticles for Sustained Oxygen Release

Hydroxyapatite Nanocoating on Calcium Peroxide Microparticles for Sustained Oxygen Release

Experimental study on the repair of spinal cord injury by conducting hydrogel loaded with tetramethylpyrazine sustained-release microparticles

To investigate the neuroprotective effect of conducting hydrogel loaded with tetramethylpyrazine sustained-release microparticles (hereinafter referred to as "TGTP hydrogel") on spinal cord injury rats. Forty-eight adult female Sprague Dawley rats were randomly divided into 4 groups: sham operation group (group A), model group (group B), conductive hydrogel group (group C), and TGTP hydrogel group (group D), with 12 rats in each group. Only laminectomy was performed in group A, and complete spinal cord transection was performed in groups B, C, and D. Basso-Bettie-Bresnahan (BBB) score was used to evaluate the recovery of hind limb motor function of each group before modeling and at 1, 3, 7, 14, and 28 days after modeling, respectively. At 28 days after modeling, the rats were sacrificed for luxol fast blue (LFB) staining to detect myelin regeneration. Nissl staining was used to detect the survival of neurons. Immunohistochemical staining was used to evaluate the expression of inflammation-related factors [nuclear factor кB (NF-кB), tumor necrosis factor α (TNF-α), and interleukin 10 (IL-10)]. Immunofluorescence staining and Western blot were used to evaluate the expression of neurofilament 200 (NF200). BBB scores of group A were significantly better than those of the other three groups at all time points after modeling (P<0.05); at 14 and 28 days after modeling, there was no significant difference in BBB scores between groups C and D (P>0.05), but the BBB score of group D was significantly better than that of group B (P<0.05). LFB staining and Nissl staining showed that the structure of neurons and myelin in group A was intact, and the myelin integrity and survival number of neurons in group D were significantly better than those in groups B and C. Immunohistochemical staining showed that the absorbency (A) value of NF-кB and TNF-α in group A were significantly lower than those in groups B and C (P<0.05), the A value of IL-10 was significantly higher than that in the other three groups (P<0.05); the A value of NF-κB in group D was significantly lower than that in groups B and C, the A value of TNF-α in group D was significantly lower than that in group B, while the A value of IL-10 in group D was significantly higher than that in group B (P<0.05). Immunofluorescence staining showed that the structure of neurons and nerve fibers in group A was clear and the fluorescence intensity was high. The fluorescence intensity of NF200 in group D was higher than that in groups B and C, and some nerve fibers could be seen. Western blot analysis showed that the relative expression of NF200 in group A was the highest, and the relative expression of NF200 in group D was significantly higher than that in groups B and C (P<0.05). The TGTP hydrogel can effectively promote the recovery of motor function in rats with spinal cord injury, and its mechanism may be related to the regulation of inflammatory response.

Industry Update, October 2022.

Industry Update, October 2022.

Bioadhesive Perivascular Microparticle-Gel Drug Delivery System for Intimal Hyperplasia Prevention: In Vitro Evaluation and Preliminary Biocompatibility Assessment.

Intimal hyperplasia (IH) is an undesirable pathology occurring after peripheral or coronary bypass surgery. It involves the proliferation and migration of vascular smooth muscle cells, leading to a reduction in the diameter of the vascular lumen, which can lead to stenosis and graft failure. Topically applied atorvastatin (ATV) has been shown to slow down this process. To be effective, the drug delivery system should remain at the perivascular site for 5-8 weeks, corresponding to the progression of IH, and be capable of releasing an initial dose of the drug followed by a sustained release. Ideally, bioadhesion would anchor the gel to the application site. To meet these needs, we encapsulated ATV in a 2-component system: a hyaluronic acid-dopamine bioadhesive gel for rapid release and biodegradable microparticles for sustained release. The system was characterized by scanning electron microscopy, rheology, bioadhesion on porcine arteries, and a release profile. The rheological properties were adequate for perivascular application, and we demonstrated superior bioadhesion and cohesion compared to the control HA formulations. The release profile showed a burst, generated by free ATV, followed by sustained release over 8 weeks. A preliminary evaluation of subcutaneous biocompatibility in rats showed good tolerance of the gel. These results offer new perspectives on the perivascular application towards an effective solution for the prevention of IH.

Nimbolide loaded sustained release microparticles as single-dose formulations for effective management of arthritis

At present, sustained-release formulations have gained immense interest in drug development for improving the pharmacokinetic and pharmacodynamic properties of drugs. Nimbolide (NMB), one of the active constituents of the Neem tree (Azadirachta indica), has been studied for its anti-carcinogenic, anti-fibrotic, and anti-inflammatory properties, but it has poor pharmacokinetic issues. This study aims for preparing an intra-articularly injectable NMB-PLGA microparticle formulation (NMB MPs) that releases NMB in a sustained fashion once localized in joints for the treatment of arthritis. The formulation was characterized by scanning electron microscope, infrared spectroscopy, and in vitro drug release profiles. The MPs were spherical as evidenced by microscopic images with a mean diameter of 9.17 ± 2.75 μm. With the drug loading of 28% of NMB, the entrapment efficiency was 71.22 ± 3.53%. The formulated MPs could extend the drug release up to 62.25 ± 6.58%in 33 days in the in vitro conditions. The in vivo therapeutic effect of NMB MPs (single dose) was investigated in comparison to NMB free drug (weekly doses) in the rat model of Complete Freund's Adjuvant (CFA) induced arthritis. The anti-arthritic activity was evaluated based on knee swelling, X-ray analysis of knee joints, histopathology scoring, and expression of various essential proteins. The observed superior protective effects can be attributed to the sustained release of NMB from NMB MPs that facilitated the maintenance of therapeutic drug levels. In conclusion, NMB MPs can be a useful injectable delivery system for enhancing therapeutic efficiency in treating joint diseases.

In-vitro trials to evaluate the efficacy of green microparticles for the control of cattle tick, Rhipicephalus (Boophilus) microplus

ABSTRACT Ticks are haematophagous ectoparasites that infest all domestic animals and humans. They gain medical and veterinary significance due to the variety of aetiological agents that they can transmit. Acaricides have played a pivotal role in tick control until the surge of resistance to most of the commonly employed acaricides. Alternate tick control strategies have since gained significant attention and semiochemical assisted tick control is one such strategy. Herein, we attempted to employ an eco-friendly strategy to lure and kill ticks. Sustained-release microparticles in the form of porous calcium alginate beads incorporating the attraction sex pheromone, 2,6-DCP, and tulsi oil were prepared, and their efficacy was assessed using petri-dish bioassay. There was 100% mortality of the larvae and partially fed males exposed to these microparticles after 24 hours of exposure.

In Vitro and In Vivo Evaluations of Berberine-Loaded Microparticles Filled In-House 3D Printed Hollow Capsular Device for Improved Oral Bioavailability.

The low oral bioavailability, short biological half-life, high dose, and frequent dosing of berberine (BBR) contribute to its restricted clinical use despite its extensive pharmacological activity. Thus, the objective of this study was to formulate sustained-release microparticles (MPs) using a pH-independent release polymer and to evaluate their potential to improve the oral bioavailability of BBR. BBR loaded MPs were prepared using the emulsion crosslinking method and evaluated for particle size, circularity, morphology, entrapment efficiency, solid-state analysis, swelling index, and in vitro BBR release study fitted with different models of release kinetics. The MPs exhibited desired particle sizes ranges between 11.09–11.62 μm and were almost spherical in shape, as confirmed by the circularity value and micrographic images. A loss of BBR crystallinity was observed after encapsulation in MPs, as evident from various solid-state analyses. The final optimized batch (F3) showed highest % BBR entrapment efficiency value of 81.63% ± 4.9. The in vitro BBR release performance in both acidic and alkaline media showed the desired sustained release behavior from the crosslinked MPs, where the maximum BBR release was observed at alkaline pH, which is in accordance with the swelling study data. In the in vivo study, the oral absorption profiles of BBR from both pristine and MPs formats were investigated using in-house prototyped 3D printed hollow capsules as a unit dose carrier. In vivo data showed sustained and prolonged absorption behavior of BBR from MPs compared to their pristine counterparts, which resulted in a cumulative increment of relative oral bioavailability to mitigate the aforementioned issues related to BBR. Graphical Supplementary InformationThe online version contains supplementary material available at 10.1208/s12249-022-02241-9.

Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Sustained Release of Vildagliptin: In Vitro and In Vivo Studies.

Spray-congealing (SPC) technology was utilized to prepare lipid-based microparticles (MP) capable of sustaining the release of Vildagliptin (VG) for use as a once-daily treatment for type 2 diabetes mellitus. VG microparticles were prepared using Compritol® and Gelucire®50/13 as lipid carriers in the presence of various amounts of Carbomer 934 NF. The lipid carriers were heated to 10 °C above their melting points, and VG was dispersed in the lipid melt and sprayed through the heated two-fluid nozzle of the spray congealer to prepare the VG-loaded MP (VGMP). The microparticles produced were then compressed into tablets and characterized for their morphological and physicochemical characteristics, content analysis, in vitro dissolution, and in vivo bioavailability studies in mixed-breed dogs. The VGMP were spherical with a yield of 76% of the total amount. VG was found to be in its semicrystalline form, with a drug content of 11.11% per tablet and a percentage drug recovery reaching 98.8%. The in vitro dissolution studies showed that VG was released from the tableted particles in a sustained-release fashion for up to 24 h compared with the immediate-release marketed tablets from which VG was completely released within 30 min. The in vivo pharmacokinetics studies reported a Cmax, Tmax, T1/2, and MRT of 118 ng/mL, 3.4 h, 5.27 h, and 9.8 h, respectively, for the SPC formulations, showing a significant difference (p < 0.05)) from the pk parameters of the immediate-release marketed drug (147 ng/mL, 1 h, 2.16 h, and 2.8 h, respectively). The area under the peak (AUC) of both the reference and tested formulations was comparable to indicate similar bioavailabilities. The in vitro–in vivo correlation (IVIVC) studies using multiple level C correlations showed a linear correlation between in vivo pharmacokinetics and dissolution parameters. In conclusion, SPC was successfully utilized to prepare a once-daily sustained-release VG oral drug delivery system.

Development of Glimepiride Loaded Sustained Release Microparticles Using Tubular Microreactor

Background: Glimepiride is a third-generation, oral anti-diabetic sulfonylurea drug, generally recommended for the treatment of type–II diabetes. A biocompatible polymer, Eudragit RS 100 is widely used for the preparation of targeted and time-controlled release of drugs. Glimepiride is encapsulated using Eudragit RS 100 for sustained release delivery. Objective: To develop sustained release microparticles of Glimepiride using microreactor technology to reduce the dosing frequency. Method: Microreactor precipitation method was used to develop sustained release microparticles of Glimepiride. Plackett-Burman design was employed for the optimization of all the parameters including the inner diameter of silicon tubing, the flow rate of solvent as well as antisolvent, length of tubing and concentration of polymer, etc. Microparticles prepared were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, Scanning electron microscopy and in vitro drug release as well as release kinetics study. Results: Placket Burman design was found to be effective for comparing more than two parameters at a time and showed the effect of parameters on design. The parameters A, B, C, D, E and J synergistically affected the encapsulation efficiency. FE-SEM demonstrated the smooth and spherical nature of particles. Fourier transformed infrared spectroscopy showed the absence of chemical interaction between polymer and drug; X-ray diffraction results showed the decrease in crystallinity of pure drug when it was transformed into encapsulated drug-loaded microparticles. The sustained drug release was observed for 12 h. Conclusion: Prepared Glimepiride loaded sustained release microparticles followed the first-order release kinetics. The developed formulation could reduce dose frequency and improve patient compliance.

A Green Approach to Producing Polymer Microparticles for Local Sustained Release of Flavopiridol

A Green Approach to Producing Polymer Microparticles for Local Sustained Release of Flavopiridol

Preparation and characterization of sustained release pirfenidone loaded microparticles for pulmonary drug delivery: Spray drying approach

Pirfenidone (PFD) is a drug of choice for the treatment of idiopathic pulmonary fibrosis. For the preparation of sustained release microparticles of PFD, Ethyl cellulose (EC 300) with Eudragit RS 100 in combination was used as encapsulating agents. The 3-level 2-factorial design was employed for the design of experiments (DoE). The spray dried microparticles were studied for their particle size distribution, surface topography, drug entrapment, in-vitro drug release, and aerodynamic performance. Compatibility between drug and excipients were evaluated by Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC). Particle morphology and size distribution were performed using Field Emission Scanning Electron Microscopy (FESEM) and Dynamic light scattering (DLS). The average particle size of the optimized PFD loaded formulation was found to be 3.99 μm. The surface topography study of the optimized formulation showed that the microparticles are nearly spherical with a smooth surface. In addition, the in-vitro aerosol performance was studied by Anderson cascade impactor and developed microparticles showed favorable aerodynamic performance (MMAD 4.25 μm) with narrow particle diameter distribution (GSD 1.52), therefore developed microparticles can be used as a dry powder for inhalation (DPI) for the targeted delivery to the lungs. In conclusion, sustained release microparticles of PFD were successfully prepared by the spray drying technique.

Carboxymethyl β-cyclodextrin grafted carboxymethyl chitosan hydrogel-based microparticles for oral insulin delivery

This study was aimed at utilizing polysaccharides for the development of effective hydrogel microparticles for oral insulin delivery that has a controlled, and sustained release to enhance paracellular transcellular absorption. Carboxymethyl β-cyclodextrin grafted carboxymethyl chitosan hydrogels (CMCD-g-CMCs) were prepared from carboxymethyl β-cyclodextrin (CMCD) and carboxymethyl chitosan (CMC) using a water-soluble carbodiimide as a crosslinker in the presence of N-hydroxysuccinimide. After synthesis, the hydrogel structures were determined via FT-IR and XRD analyses. The porous structure of hydrogels was confirmed by SEM observations and swelling behaviours. The insulin release behaviours were found to betriggered by pH in vitro. Results showed that insulin was successfully retained inside the hydrogels in the gastric environment and slowly released following passage to intestinal conditions. The stability of the secondary structure of insulin was studied by dichroism circular (CD) and fluorescence (FL) spectrophotometer measurement. There was no significant difference in the secondary structure between the native and released insulin. In vitro studies revealed that the hydrogel microparticles exhibited non-cytotoxicity and were transported across the Caco-2 cell monolayers mainly via the paracellular pathway. In order to examine the effectiveness of hydrogel-based sustained release microparticles in delivering insulin in vivo, we administered different insulin-loaded hydrogel microparticles to diabetic mice. In these studies, we found that the insulin-loaded hydrogel microparticles provided a significant and sustained (ranging from 6 h to 12 h) reduction in the blood glucose levels of diabetic mice compared with subcutaneous injection. Overall, these findings demonstrate that CMCD-g-CMCs may be a promising protein carrier for use in oral drug delivery.

Easy to Swallow “Instant” Jelly Formulations for Sustained Release Gliclazide Delivery

It is a challenge to safely administer sustained release medicines to patients with dysphagia. Sustained release tablets must not be crushed and multiparticulates with large particle sizes cause gritiness reducing patient acceptability. The aim of this study was to develop “instant” jellies as delivery vehicles incorporating sustained release microparticles for patients with dysphagia. Dry powder mixtures containing gelling agents such as sodium alginate and calcium ions were hydrated in 20 mL of water and formed a jelly texture within 10 min. The “instant” jellies demonstrated comparable properites to commercial “read-to-eat” jellies in appearance, rheological/textural properties and in vitro swallowing performance in an artificial throat model. Gliclazide sustained release microparticles were produced by fluidized bed coating using Eudragit® NM 30 D and achieved 99% production yield and final coated particle size (D50) of 198 ± 4.3 μm. Sustained gliclazide release was achieved over 15 h and the incorporation of the particles into the jellies significantly decreased the drug release rate. This novel drug delivery system offers a patient-centric solution to the long-standing challenge of administering sustained release medicines to patients with dysphagia and can potentially be used for paediatric patients.