25-Hydroxyvitamin D3-Loaded PLA Microspheres: In Vitro Characterization and Application in Diabetic Periodontitis Models

This study aimed at the preparation of a sustained-release 25-hydroxyvitamin D₃ (25OHD) treatment for diabetic periodontitis, a known complication of diabetes. 25OHD-loaded polylactic acid (PLA) microspheres were prepared using oil-in-water emulsion–solvent evaporation method. The prepared microspheres exhibited intact surfaces, with average sizes ranging from 42.3 to 119.4 μm. The encapsulation efficiency ranged from 79.2% (w/w) to 88.5% (w/w), and the drug content was between 15.8% (w/w) and 17.8% (w/w). Drug release from the produced microspheres followed a near-to-zero-order release pattern and lasted over 10 weeks. In an in vitro model of diabetic periodontitis, the abnormal morphological changes and the decrease in the cell viability of bone marrow stromal cells could be effectively attenuated after the 25OHD-loaded microsphere application. Additionally, in a rat model of diabetic periodontitis, alveolar bone loss was inhibited and osteoid formation in the periodontium was promoted upon 25OHD-loaded microsphere treatment. In conclusion, 25OHD-loaded PLA microspheres may provide an effective approach for the treatment of this disease.     

Sustained-Release Delivery of Octreotide from Biodegradable Polymeric Microspheres

The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR^® formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague–Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR^® all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40–130 pg/10 μL and 20–100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR^® every 28 days and every 42 days at a dose of 3 mg/rat, respectively.     

Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.     

Chitosan/Polyethylene Glycol Beads Crosslinked with Tripolyphosphate and Glutaraldehyde for Gastrointestinal Drug Delivery

This study reports on the preparation of chitosan (CS)/polyethylene glycol (PEG) hydrogel beads using sodium diclofenac (DFNa) as a model drug. Following the optimization of the polymer to drug ratio, the chitosan beads were modified by ionic crosslinking with sodium tripolyphosphate (TPP). The CS/PEG/DFNa beads obtained from a (w/w/w) ratio of 1/0.5/0.5 with crosslinking in 10% (w/v) TPP at pH 6.0 for 30 min yielded excellent DFNa encapsulation levels with over 90% loading efficiency. The dissolution profile of DFNa from CS/PEG/DFNa beads demonstrated that this formulation was able to maintain a prolonged drug release for approximately 8 h. Among the formulations tested, the CS/PEG/DFNa (1/0.5/1 (w/w/w)) beads crosslinked with a combination of TPP (10% (w/v) for 30 min) and glutaraldehyde (GD) (5% (w/v)) were able to provide minimal DFNa release in the gastric and duodenal simulated fluids (pH 1.2 and 6.8, respectively) allowing for a principally gradual drug release over 24 h in the intestinal (jejunum and ileum) simulated fluid (pH 7.4). Thus, overall the CS/PEG beads crosslinked with TPP and GD look to be a promising and novel alternative gastrointestinal drug release system.     

Effect of Rheology and Poloxamers Properties on Release of Drugs from Silicon Dioxide Gel-Filled Hard Gelatin Capsules—A Further Enhancement of Viability of Liquid Semisolid Matrix Technology

The liquid and semisolid matrix technology, filling liquids, semi-solids and gels in hard gelatin capsule are promising, thus, there is a need of enhanced research interest in the technology. Therefore, the present study was aimed to investigate isoniazid (freely soluble) and metronidazole (slightly soluble) gels filled in hard gelatin capsules for the effect of poloxamers of different viscosities on release of the drugs. Gel of each drug (10% w/w, particle size 180–250 μm), prepared by mixing poloxamer and 8% w/w hydrophilic silicon dioxide (Aerosil® A200), was assessed for rheology, dispersion stability and release profile. Both the drugs remained dispersed in majority of gels for more than 30 days, and dispersions were depended on gels’ viscosity, which was further depended on viscosity of poloxamers. A small change in viscosity was noted in gels on storage. FTIR spectra indicated no interactions between components of the gels. The gels exhibited thixotropic and shear-thinning behaviour, which were suitable for filling in hard gelatin capsules without any leakage from the capsules. The release of both drugs from the phase-stable gels for 30 days followed first-order kinetics and was found to be correlated to drugs’ solubility, poloxamers’ viscosity, polyoxyethylene contents and proportion of block copolymer (poloxamers) in the gels. The findings of the present study indicated that release of drugs of different solubilities (isoniazid and metronidazole) might be modified from gels using different poloxamers and Aerosil® A200.     

Development of an Ibuprofen‐releasing biodegradable PLA/PGA electrospun scaffold for tissue regeneration

Our aim was to develop a biodegradable fibrous dressing to act as a tissue guide for in situ wound repair while releasing Ibuprofen to reduce inflammation in wounds and reduce pain for patients on dressing changes. Dissolving the acid form of Ibuprofen (from 1% to 10% by weight) in the same solvent as 75% polylactide, 25% polyglycolide (PLGA) polymers gave uniformly loaded electrospun fibers which gave rapid release of drug within the first 8 h and then slower release over several days. Scaffolds with 10% Ibuprofen degraded within 6 days. The Ibuprofen released from these scaffolds significantly reduced the response of fibroblasts to major pro‐inflammatory stimulators. Fibroblast attachment and proliferation on scaffolds was unaffected by the addition of 1–5% Ibuprofen. Scaffolds loaded with 10% Ibuprofen initially showed reduced cell attachment but this was restored by soaking scaffolds in media for 24 h. In summary, addition of Ibuprofen to electrospun biodegradable scaffolds can give acute protection of adjacent cells to inflammation while the scaffolds provide an open 3D fibrous network to which cells can attach and migrate. By 6 days, such scaffolds will have completely dissolved into the wound bed obviating any need for dressing removal. Biotechnol. Bioeng. 2010; 105: 396–408. © 2009 Wiley Periodicals, Inc.     

Evaluation of mucoadhesive hydrogels loaded with diclofenac sodium-chitosan microspheres for rectal administration

Considering the advantageous for the rectal administration of non-steroidal anti-inflammatory drugs, the objective of this study was to formulate and evaluate rectal mucoadhesive hydrogels loaded with diclofenac-sodium chitosan (DFS-CS) microspheres. Hydroxypropyl methylcellulose (HPMC; 5%, 6%, and 7% w/w) and Carbopol 934 (1% w/w) hydrogels containing DFS-CS microspheres equivalent to 1% w/w active drug were prepared. The physicochemical characterization revealed that all hydrogels had a suitable pH for rectal application (6.5–7.4). The consistency of HPMC hydrogels showed direct proportionality to the concentration of the gelling agent, while carbopol 934 gel showed its difficulty for rectal administration. Farrow’s constant for all hydrogels were greater than one indicating pseudoplastic flow. In vitro drug release from the mucoadhesive hydrogel formulations showed a controlled drug release pattern, reaching 34.6–39.7% after 6 h. The kinetic analysis of the release data revealed that zero-order was the prominent release mechanism. The mucoadhesion time of 7% w/w HPMC hydrogel was 330 min, allowing the loaded microspheres to be attached to the surface of rectal mucosa. Histopathological examination demonstrated the lowest irritant response to the hydrogel loaded with DFS-CS microspheres in response to other forms of the drug.     

Using drug-loaded pH-responsive poly(4-vinylpyridine) microspheres as a new strategy for intelligent controlling of <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> contamination in bioethanol fermentation

Bioethanol fermentation is usually contaminated by bacteria, especially lactic acid bacteria (LAB), thereby leading to decrease of bioethanol yield and serious economic losses. Nisin is safer for controlling of bacterial contamination than antibiotics that are widely applied in industry. Moreover, in LAB contaminative bioethanol fermentation system, consistently decreased pH value provides opportunity to realize pH value responsive material-based release of anti-bacteria substances for intelligent and persistent controlling of bacterial contamination. In this study, nisin was embedded into pH-sensitive poly(4-vinylpyridine) (P4VP) microspheres synthesized by suspension polymerization to realize intelligent controlling of Lactobacillus plantarum contamination in bioethanol fermentation. Chloramphenicol with the highest antimicrobial activity and excellent stability was chosen as the model drug to be embedded into P4VP microspheres to test the drug release behavior. The drug release curve of chloramphenicol-loaded P4VP microspheres showed sustained and pH-responsive release properties. The diameters of the microspheres ranged from 40 to 100 µm. The encapsulation efficiency of nisin into P4VP microspheres was 47.67% and the drug-loading capacity of nisin was 2.5%. Nisin-loaded P4VP microspheres were added into the simulated contaminative fermentation system, and successfully reversed the decline of bioethanol yield secondary to L. plantarum contamination. The results in this study indicated that L. plantarum contamination in bioethanol fermentation could be effectively controlled by nisin-loaded P4VP microspheres.     

Derivation of an Analytical Solution to a Reaction-Diffusion Model for Autocatalytic Degradation and Erosion in Polymer Microspheres

A mathematical reaction-diffusion model is defined to describe the gradual decomposition of polymer microspheres composed of poly(D,L-lactic-co-glycolic acid) (PLGA) that are used for pharmaceutical drug delivery over extended periods of time. The partial differential equation (PDE) model treats simultaneous first-order generation due to chemical reaction and diffusion of reaction products in spherical geometry to capture the microsphere-size-dependent effects of autocatalysis on PLGA erosion that occurs when the microspheres are exposed to aqueous media such as biological fluids. The model is solved analytically for the concentration of the autocatalytic carboxylic acid end groups of the polymer chains that comprise the microspheres as a function of radial position and time. The analytical solution for the reaction and transport of the autocatalytic chemical species is useful for predicting the conditions under which drug release from PLGA microspheres transitions from diffusion-controlled to erosion-controlled release, for understanding the dynamic coupling between the PLGA degradation and erosion mechanisms, and for designing drug release particles. The model is the first to provide an analytical prediction for the dynamics and spatial heterogeneities of PLGA degradation and erosion within a spherical particle. The analytical solution is applicable to other spherical systems with simultaneous diffusive transport and first-order generation by reaction.     

Preparation of biodegradable microspheres and matrix devices containing naltrexone

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices.     

Novel Strategy to Fabricate Floating Drug Delivery System Based on Sublimation Technique

The present study aims to develop floating drug delivery system by sublimation of ammonium carbonate (AMC). The core tablets contain a model drug, hydrochlorothiazide, and various levels (i.e., 0–50% w/w) of AMC. The tablets were then coated with different amounts of the polyacrylate polymers (i.e., Eudragit® RL100, Eudragit® RS100, and the mixture of Eudragit® RL100 and Eudragit® RS100 at 1:1 ratio). The coated tablets were kept at ambient temperature (25°C) or cured at 70°C for 12 h before further investigation. The floating and drug release behaviors of the tablets were performed in simulated gastric fluid USP without pepsin at 37°C. The results showed that high amount of AMC induced the floating of the tablets. The coated tablets containing 40 and 50% AMC floated longer than 8 h with a time-to-float of about 3 min. The sublimation of AMC from the core tablets decreased the density of system, causing floating of the tablets. The tablets coated with Eudragit® RL100 floated at a faster rate than those of Eudragit® RS100. Even the coating level of polymer did not influence the time-to-float and floating time of coated tablets containing the same amount of AMC, the drug release from the tablets coated with higher coating level of polymer showed slower drug release. The results suggested that the sublimation technique using AMC is promising for the development of floating drug delivery system.     

Taste Masking by Spray-Drying Technique

The purpose of this research was to develop the taste-masked microspheres of intensely bitter drug ondansetron hydrochloride (OSH) by spray-drying technique. The bitter taste threshold value of OSH was determined. Three different polymers viz. Chitosan, Methocel E15 LV, and Eudragit E100 were used for microsphere formation, and the effect of different polymers and drug–polymer ratios on the taste masking and release properties of microspheres was investigated. The microspheres were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, Drug loading, in vitro bitter taste evaluation, and drug-release properties. The taste masking was absent in methocel microspheres at all the drug–polymer ratios. The Eudragit microspheres depicted taste masking at 1:2 drug–polymer ratio whereas with Chitosan microspheres the taste masking was achieved at 1:1 drug–polymer ratio. The drug release was about 96.85% for eudragit microspheres and 40.07% for Chitosan microspheres in 15 min.     

Development and Optimisation of Spironolactone Nanoparticles for Enhanced Dissolution Rates and Stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ～170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.     

Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers

The present investigation was undertaken to fabricate modified transport fluconazole transdermal spray using ethyl cellulose and Eudragit® RS100 as film-forming polymers. Eudragit® RS100 (X ₁) and ethyl cellulose (X ₂) were selected as independent variables in 3² full factorial design, whereas drug transport in first hour (Y ₁) and the time required for 50% drug transport (Y ₂) were selected as dependent variables. Eutectic blend of camphor and menthol was used as permeation enhancer cum solvent for film-forming polymers. The pH, viscosity, volume of solution delivered upon each actuation, spray angle, ex–in vivo physical evaluation and in vitro drug transport of the formulated products were evaluated. The optimized batch B16 containing 5.25% w/w ethyl cellulose and 10.6% w/w Eudragit® RS100 was formulated by overlapping the contour plots of Y ₁ and Y ₂. The pH, viscosity, volume of solution sprayed upon each actuation and spray angle of the batch B16 was 6.3, 52.9 cPs, 0.24 ml and 82.6° respectively. The film of optimized batch was flexible and dermal-adhesive. The responses Y ₁ and Y ₂ of batch B16 were 7.91 μg/ml and 347 min respectively. The kinetics of drug transport was best explained by the Korsmeyer and Peppas model. The eutectic mixture consisting of equal parts of camphor and menthol showed improved drug permeation through shed snake skin. Short-term stability study demonstrated insignificant changes in performance characteristics.     

Formulation and <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4?×?2² factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X ₁), drug–lipid ratio (X ₂), and filler type (X ₃) on the percentage drug released at 8, 12, and 24 h (Y ₁, Y ₂, and Y ₃) as dependent variables. Sixteen TBS sustained-release matrices (F1–F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug–Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.     

Controlled Release of Dutasteride from Biodegradable Microspheres: In Vitro and In Vivo Studies

The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH), into poly(lactide-co-glycolide) (PLGA). A response surface method (RSM) with central composite design (CCD) was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods.     

Injectable Supramolecular Hydrogel from Insulin-Loaded Triblock PCL-PEG-PCL Copolymer and γ-Cyclodextrin with Sustained-Release Property

Supramolecular hydrogels formed by cyclodextrins and polymers have been widely investigated as a biocompatible, biodegradable and controllable drug delivery system. In this study, a supramolecular hydrogel based on biodegradable poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL-PEG-PCL) triblock copolymers and γ-cyclodextrin (γ-CD) was prepared through inclusion complexation as an injectable, sustained-release vehicle for insulin. The triblock copolymer PCL-PEG-PCL was synthesised by the ring-opening polymerisation method, using microwave irradiation. The polymerisation reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The supramolecular hydrogel was prepared in aqueous solution by blending an aqueous γ-CD solution with an aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. In vitro insulin release through the hydrogel system was studied. The relative surface hydrophobicity of standard and released insulin from the SMGel was estimated using 8-anilino-1-naphthalene sulfonic acid (ANS). Results of ¹HNMR and gel permeation chromatography revealed that microwave irradiation is a simple and reliable method for synthesis of PCL-PEG-PCL copolymer. Gelation occurred within a minute. The supramolecular hydrogel obtained by mixing 10.54% (w/v) γ-CD and 2.5% (w/v) copolymer had an excellent syringeability. Insulin was released up to 80% over a period of 20 days. Insulin kept its initial folding after formulating and releasing from SMGel. A supramolecular hydrogel based on complexation of triblock PCL-PEG-PCL copolymer with γ-cyclodextrin is a suitable system for providing sustained release of therapeutic proteins, with desirable flow behaviour.Key words: insulin, PCL-PEG-PCL, supramolecular hydrogel, triblock copolymer, γ-CD     

Phytantriol-Based In Situ Liquid Crystals with Long-Term Release for Intra-articular Administration

The purpose of this study was to develop an injectable in situ liquid crystal formulation for intra-articular (IA) administration, and in situ forming a viscous liquid crystalline gel with long-term release of sinomenine hydrochloride (SMH) upon water absorption. The pseudo-ternary phase diagram of phytantriol (PT)-ethanol (ET)-water was constructed, and isotropic solutions were chosen for further optimization. The physicochemical properties of isotropic solutions were evaluated, and the phase structures of liquid crystalline gels formed by isotropic solutions in excess water were confirmed by crossed polarized light microscopy (CPLM) and small-angle X-ray scattering (SAXS). In vitro drug release studies were conducted by using a dialysis membrane diffusion method. The optimal in situ cubic liquid crystal (ISV₂) (PT/ET/water, 64:16:20, w/w/w) loaded with 6 mg/g of SMH showed a suitable pH, showed to be injectable, and formed a cubic liquid crystalline gel in situ with minimum water absorption within the shortest time. The optimal ISV₂ was able to sustain the drug release for 6 days. An in situ hexagonal liquid crystal (ISH₂) system was prepared by addition of 5% vitamin E acetate (VitEA) into PT in the optimal ISV₂ system to improve the sustained release of SMH. This ISH₂ (PT/VitEA/ET/water, 60.8:3.2:16:20, w/w/w/w) was an injectable isotropic solution with a suitable pH range. The developed ISH₂ was found to be able to sustain the drug release for more than 10 days and was suitable for IA injection for the treatment of rheumatoid arthritis (RA).KEY WORDS: in situ cubic liquid crystal, in situ hexagonal liquid crystal, phytantriol, sinomenine hydrochloride, sustained drug release     

Design and Concept of Polyzwitterionic Copolymer Microgel Drug Delivery Systems <Emphasis Type="Italic">In Situ</Emphasis> Loaded with Non-steroidal Anti-inflammatory Ibuprofen

Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer micro- and nano-sized drug delivery carriers. In this respect, the use of hydrogel carriers based on polyzwitterions (PZIs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of micro-structured p(VA-co-DMAPS) systems with different compositions in situ loaded with Ibuprofen by emulsifier-free emulsion copolymerization (EEC) in water. The mean size of the prepared microparticles was measured by SEM and particles have been visualized by AFM. The inclusion of Ibuprofen in the polyzwitterionic copolymer microgel systems was established by using DSC. In vitro drug release experiments were carried out in order to estimate the ability of the obtained microgels to modify the release of water-insoluble Ibuprofen.     

Cellulose-Based Matrix Microspheres of Prednisolone Inclusion Complex: Preparation and Characterization

The purpose of the present investigation was to encapsulate pure prednisolone (PRD) and PRD–hydroxypropyl-β-cyclodextrin (HPβCD) complex in cellulose-based matrix microspheres. The system simultaneously exploits complexation technique to enhance the solubility of low-solubility drug (pure PRD) and subsequent modulation of drug release from microspheres (MIC) at a predetermined time. The microspheres of various compositions were prepared by an oil-in-oil emulsion–solvent evaporation method. The effect of complexation and presence of cellulose polymers on entrapment efficiency, particle size, and drug release had been investigated. The solid-state characterization was performed by Fourier transform infrared spectroscopy, thermogravimetry, differential scanning calorimetry, and powder X-ray diffractometry. The morphology of MIC was examined by scanning electron microscopy. The in vitro drug release profiles from these microspheres showed the desired biphasic release behavior. After enhancing the solubility of prednisolone by inclusion into HPβCD, the drug release was easily modified in the microsphere formulation. It was also demonstrated that the CDs in these microspheres were able to modulate several properties such as morphology, drug loading, and release properties. The release kinetics of prednisolone from microspheres followed quasi-Fickian and first-order release mechanisms. In addition to this, the f ₂-metric technique was used to check the equivalency of dissolution profiles of the optimized formulation before and after stability studies, and it was found to be similar. A good outcome, matrix microspheres (coded as MIC5) containing PRD–HPβCD complex, showed sustained release of drug (95.81%) over a period of 24 h.