Effects of formulation properties on sol–gel behavior of chitosan/glycerolphosphate hydrogel

Chitosan solution containing glycerolphosphate disodium salt (Gp) is an injectable thermosensitive in situ gel-forming system which undergoes sol–gel transition under certain physiological pH and temperature conditions. When a drug-incorporated chitosan/Gp solution is injected into the body, it forms a three-dimensional gel at 37 °C, which allows the drug to be released in a sustained manner. This hydrogel can be used as a drug delivery system for prolonged release of peptides and glycopeptides. The objective of this work was to investigate the effect of different excipients on the sol–gel behavior of this thermosensitive hydrogel. Chitosan polymeric solutions (2 % w/v) containing Gp and different excipients, such as hydroxypropyl methyl cellulose (HPMC), polyethylene glycol (PEG) with two different molecular weights (PEG200 and PEG1000), and poloxamer (F127) in various concentrations, were prepared, and the pH, sol–gel transition time, and syringeability of the final solutions were evaluated. The obtained results point to HPMC as the best additive for chitosan/Gp solutions in developing an in situ gel-forming drug delivery system with optimum gelling time. A significant decrease was noted in the sol-to-gel transition time (from 90 to 60 s) when HPMC was added to the system. This may have been due to the HPMC structure which acted as a viscosity-enhancing and gel-promoting agent. The in vitro release of vancomycin hydrochloride from chitosan/Gp/HPMC hydrogel was also studied. Vancomycin release studies showed a sustained release profile for over 20 days. It can be concluded that combining chitosan/Gp and HPMC is a promising strategy for preparing a thermally reversible in situ gel-forming delivery system with an optimized gelation time.     

Construction and evaluation of the hydroxypropyl methyl cellulose-sodium alginate composite hydrogel system for sustained drug release

We prepared a hydroxypropyl methyl cellulose-sodium alginate (HPMC-SA) composite hydrogel with a membrane covering the semi-interpenetrating network based on a semi-synthetic polymer hydroxypropyl methyl cellulose (HPMC) and a natural polymer sodium alginate (SA) by Ca²⁺ crosslinking and polyelectrolyte complexation with chitosan (CS) covering the hydrogel surface. The physiochemical properties of HPMC-SA hydrogels were evaluated by scanning electron microscopy, infrared spectrum, X-ray diffraction, and thermogravimetric analysis. The swelling ratio of the HPMC-SA composite hydrogel in simulated gastrointestinal fluid was measured. The drug release behavior of the HPMC-SA composite hydrogel for macro-molecular and small-molecule drugs was evaluated by using bovine serum albumin, metformin hydrochloride, and indomethacin as model drugs. The results showed that the HPMC-SA hydrogel had good water absorption and degradability, an increased swelling ratio of 55, and a prolonged time for maximum swelling degree of 50 h. Moreover, the hydrogel exhibited higher drug-loading capacity and improvements in the sustained release of bio-macromolecules, demonstrating its potential as a drug carrier for biomedical applications.     

PCL microsphere/PEG-based composite hydrogels for sustained release of methadone hydrochloride

Hydrogels have increasingly received considerable attention for local opioids delivery in order to sustained wound pain relief. However, burst release of drugs is a critical problem of hydrogels. To this aim, a local drug delivery system consisting of polycaprolactone (PCL) microspheres containing methadone hydrochloride/polyethylene glycol (PEG)-based hydrogels were developed to prolong drug release with potential utilization in pain treatment. Four different drug delivery systems, including methadone hydrochloride/PEG-(N₃)₄-based hydrogel, methadone hydrochloride/PEG-(N₃)₂-based hydrogel, methadone hydrochloride/PCL/PEG-(N₃)₄, and methadone hydrochloride/PCL/PEG-(N₃)₂ composite hydrogels, were fabricated to investigate drug release profiles of these systems. The results showed that drug released can be controlled by both the double-barrier matrix (hydrogel/microsphere), and the crosslinking density of hydrogels. Therefore, methadone hydrochloride/PCL/PEG-(N₃)₂ composite hydrogel with high crosslinking density has great potential application in sustained release systems for wound pain relief. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48967.     

Development of Sodium Carboxymethyl Cellulose-based Poly(acrylamide-co-2acrylamido-2-methyl-1-propane sulfonic acid) Hydrogels for In Vitro Drug Release Studies of Ranitidine Hydrochloride an Anti-ulcer Drug

The formation of sodium carboxymethyl cellulose (SCMC) based semi-interpenetrating networks (semi-IPN) with poly(acylamide-co-2-acrylamido-2-methy-l-propanesulfonic-acid) hydrogels. The hydrogels were prepared by free-radical polymerization using redox initiator. The characterizations of hydrogels were done by swelling experiments, FTIR spectroscopy and DSC analysis. Morphology of the samples were examined by SEM. Experimental results indicate that the semi-IPN hydrogel containing 0.10 g of SCMC and 5.829 mM of AMPS, shows the highest swelling capacity (64.83 g/g). The swelling behavior of the semi-IPN hydrogel (AS5) was studied in different pH solutions. The ranitidine hydrochloride drug loading and release of the semi-IPN hydrogels were studied by using a UV spectrophotometer.     

Controlled release of Montelukast Sodium from pH-sensitive injectable hydrogels

pH sensitive hydrogels showed excellent drug release properties, with promise for other biomedical applications. Also, the impact of molecular weight (MW) and degree of deacetylation (DDA) of chitosan on the fabricated chitosan/poly (vinyl alcohol) (3:1 mol ratio) hydrogel with selective silane crosslinker amount was evaluated for controlled drug delivery. The FTIR spectroscopy confirmed the incorporated components and the developed interactions among the polymer chains. The hydrogel characteristics were expressed by their responsive behaviour in different environments (water, ionic media and pH). The hydrogel sample (CH1000) having chitosan with higher MW and DDA exhibited more thermal stability and bacterial growth inhibition against E.coli. All hydrogels exhibited maximum swelling at basic and neutral pH and less swelling was observed in acidic media. For drug release analysis performed in simulated gastric fluid, hydrogel showed controlled drug release in 2 h but it was more than 10%, consequently cannot be used for oral purpose. In simulated intestinal fluid, hydrogels exhibited more than 80% release within 90 min. This characteristic phenomenon at neutral pH empowered hydrogel appropriate towards injectable and targeted controlled release of applicable drug. It was concluded that the prepared hydrogel can be administered directly into the venous circulation through syringe and can be used with better results for biomedical applications.     

Characterization and Application of Intercalated Montmorillonite with Verapamil and its Polymethyl Methacrylate Nanocomposite in Drug Delivery

This work examined two drug delivery systems: the first system studied the adsorption of Verapamil hydrochloride drug into montmorillonite clay (MMT) by intercalation process to prepare MMT-Verapamil hybrid at different intercalating time, temperatures, pH values and initial drug concentrations. The second system includes the preparation of MMT-Verapamil hybrid combined with polymethyl methacrylate via an emulsion polymerization process to produce a novel nanocomposite material to be used in drug delivery. The polymerization process was carried out using an ultrasonic technique to achieve a biologically safe drug delivery system. Best conditions for the intercalation of verapamil hydrochloride drug into the interlayer of MMT clay were found to be at 50°C and 1 hr using pH ranges of 4–6. The prepared MMT-Verapamil hybrid and the produced MMT-verapamil-MMA nanocomposite material were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and thermal gravimetric analysis (TGA). The in-vitro release profile of Verapamil in the case of a drug hybrid is faster than the release in the case of a drug nanocomposite in both gastric and intestinal fluids where, in the case of gastric fluid (pH 1.2), about 40% of the loaded drug was released from the drug hybrid in the first 4 h against only 37% in 5 h in the case of drug nanocomposite. Also in the intestinal fluid (pH 7.4), the verapamil release from drug hybrid reached 68% in 5 h against only 57% was released from drug nanocomposites in 7 h.     

Controlled release of berberine hydrochloride from alginate microspheres embedded within carboxymethyl chitosan hydrogels

Berberine hydrochloride is a natural medicine with wide clinical application. In this article, berberine hydrochloride was entrapped into alginate microspheres via an emulsification/gelation method. The size distribution of the microspheres was determined by a laser particle sizer. Drug distribution within the microspheres was determined by confocal laser scanning microscopy. Those drug‐loaded microspheres were further entrapped into carboxymethyl chitosan (CMC) hydrogel to form a new drug‐delivery system (DDS). The surface morphology of the DDS was observed using metallographic microscopy and scanning electron microscopy (SEM). The compression strength of the DDSs with alginate microspheres was found significantly higher than that of the pure hydrogel. The drug‐release performances of the DDS in phosphate buffer solution (PBS, pH 7.4), saline solution (pH 6.3), and hydrochloric acid solution (HAS, pH 1.2) were also studied. Decay of the DDS in PBS within 72–80 h results in a faster release; however, the steady release in saline solution could last for all the testing period without cleavage of the DDS. In HAS, because of the shrinkage of the DDS, release is fast in the first period and remains steady later. The DDS exhibits prospective in controlled steady release of drugs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

In-Vitro Release Study of Metoprolol Succinate from the Bioadhesive Films of Pullulan-Polyacrylamide Blends

In the present work, an attempt has been made to investigate the drug release profile of pullulan-polyacrylamide blend films with metoprolol succinate as a model drug. The drug diffusion behavior of pullulan/polyacrylamide films has been established by an open glass diffusion cell at 37 ± 1°C. The diffusion rate of the drug was determined by UV/visible spectroscopy. The kinetics of drug release are fitted to the Higuchi and Koresmeyer–Peppas model. The drug release kinetics for the blend was found to be fast and follows Fickian mechanism. This blend could be a promising approach for formulating a transdermal drug delivery system for immediate release with good film-forming property.     

pH-/temperature-sensitive carboxymethyl chitosan/poly(N-isopropylacrylamide-co-methacrylic acid) IPN: preparation,characterization and sustained release of riboflavin

Dual crosslinked pH-/temperature-sensitive interpenetrating polymer networks (IPN) were prepared by free-radical copolymerization of N-isopropylacrylamide and methylacrylic acid (MAA) using N,N′-methylenebisacrylamide as a crosslinker in carboxymethyl chitosan (which was crosslinked by Ca²⁺) aqueous solution. Scanning electron microscopy was used to observe the morphologies of the IPN at different pH values and temperatures. The effects of MAA content and environmental pH on the “pH-/temperature-induced” phase transition behavior of the IPN hydrogels were investigated. The phase transition temperature was adjusted to 37 °C by changing the MAA content. The effects of drug-loaded content, crosslinking density, environmental pH, and temperature on the drug release behavior of the drug-loaded IPN hydrogel were also explored. Based on results, the hydrogel possessed pH/temperature sensitivity. The swelling ratio and phase translation temperature of the hydrogel were lower at lower pH. These values were lowest at pH 3.0. The release behavior of riboflavin was dependent on preparation condition, environmental pH, and temperature. Drug cumulative release was only 6 % at pH 1.8 for 2 h. The drug cumulative release was 13 % before the drug-loaded hydrogel reached the position with pH 6.8. The drug release rate was higher at lower temperature. Therefore, dual-crosslinked hydrogel holds much potential as a drug site-specific carrier.     

Self‐Healing,Injectable Gelatin Hydrogels Cross‐Linked by Dynamic Schiff Base Linkages Support Cell Adhesion and Sustained Release of Antibacterial Drugs

A new class of dynamic hydrogels made through Schiff base bonds based on gelatin (type A and B) and polyethylene glycol dibenzaldehyde (diBA‐PEG, 2000 and 4000 g mol^?1) is developed. Hydrogels form in situ by mixing aqueous solutions of gelatin and diBA‐PEG at a carefully adjusted pH. Compression test shows that the samples based on gelatin A are able to withstand at least ten cyclic loading/unloading without crack formation and significant permanent deformation. Self‐healing behavior of the hydrogel is proved by rheological measurements and also visual method. This hydrogel is proven to be injectable and nontoxic. Performance of the hydrogel in loading and delivery of clindamycin hydrochloride, as an antibacterial model drug, is evaluated against Staphylococcus aureus via antibacterial activity test. In vitro release of clindamycin hydrochloride is studied through an innovative method and it becomes clear that the release of clindamycin hydrochloride from this hydrogel follows a zero‐order kinetics.     

Synthesis of hydrogel for drug delivery studies utilizing photoinitiator‐free photopolymerization based on the donor/acceptor pair,N‐vinylpyrrolidinone and hydroxypentyl maleimide

Photo‐differential scanning calorimetry (photo‐DSC) was used to study the rate of photoinitiator‐free copolymerization of a donor/acceptor pair involving N‐vinylpyrrolidinone (NVP), and a water‐soluble N‐substituted maleimide, hydroxypentyl maleimide (HPMI). Glucose, 1,1‐diethoxy ethane (DEE) and isopropyl alcohol (IPA) were included for the evaluation of their efficiencies as hydrogen donors, and glucose was shown to be the most efficient in enhancing the rate of polymerization. This photoinitiator (PI)‐free system was extended to hydrogel preparation using the radiation method with UV as the radiation source based on the same donor/acceptor pair, ie NVP/HPMI, in the presence of glucose as the hydrogen donor. Swelling and drug release tests showed that this hydrogel exhibited high swelling ability and a rather fast drug release rate when using theophylline as the model drug. These tests also revealed that the drug release kinetics and the water diffusion into this hydrogel did not adhere to the Fickian model. Cytotoxicity testing showed no evidence of this hydrogel being cytotoxic. © 2002 Society of Chemical Industry     

Cotton gauze-hydrogel composites: Valuable tools for electrically modulated drug delivery

Cotton gauze was inserted into a hydrogel network composed of acrylamide, sodium methacrylate, and polyethylene glycol dimethacrylate to fabricate an electroresponsive delivery system for wound dressing. The composite was characterized by swelling measurements, showing that shrinking or swelling depend on the applied voltage. The release profile of incorporated diclofenac sodium salt shows the possibility to modulate the kinetics by changes in the amplitude and duration of applied electric pulses. Mathematical models allow a characterization of release profiles, which are slower when an external voltage of 6, 12, and 18 V is applied, and faster at 24 V.     

Cumulative release of cefotaxim from interpenetrating networks of poly(vinyl alcohol-g-acrylamide) and chitosan-g-polyacrylamide chains

In this study, novel interpenetrating networks comprising of poly(vinyl alcohol-g-acrylamide) and chitosan-g-polyacrylamide chains were designed by redox polymerization method and their potential for controlled release of an antibiotic drug cefotaxim, and antibacterial and cytotoxic behaviors were evaluated. The polymer matrix hydrogel was loaded with cefotaxim drug by allowing it to swell in the drug solution reservoirs of concentrations varying in the range 0.1–0.5 mg/mL. The polymer network was examined by FTIR, SEM and DSC techniques for structural, morphological and thermal characterization. The FTIR spectra clearly confirmed the presence of functional groups of constituent polymers; the SEM image suggested a mesh-type morphology with approximate mesh dimensions of 10 μm × 20 μm. The DSC studies revealed a fall in glass transition temperature (Tg) of both chitosan and poly(vinyl alcohol) to 50 and 70 °C, respectively, from their native values. The release studies were performed in PBS (pH 7.4) under in vitro conditions and the drug release kinetics was investigated. It was found that the amount of drug released increases from 5.4 to 8.4 mg when the drug loading increases from 5.0 to 16.0 %. It was also found that when the pH rises from 1.8 to 7.4, an increase in drug release was noticed, while a further increase in pH to 8.6 resulted in a fall in the amount of released drug. The polymer matrix also showed fair antibacterial properties against E. coli and no cytotoxicity for L-929 mouse fibroblast cells.     

Temperature/pH/magnetic triple‐sensitive nanogel–hydrogel nanocomposite for release of anticancer drug

Hydrogels, nanogels and nanocomposites show increasing potential for application in drug delivery systems due to their good chemical and physical properties. Therefore, we were encouraged to combine them to produce a new compound with unique properties for a long‐term drug release system. In this regard, the design and application of a nanocomposite hydrogel containing entrapped nanogel for drug delivery are demonstrated. To this aim, we first prepared an iron oxide nanocomposite nanogel based on poly(N‐isopropylacrylamide)‐co‐((2‐dimethylaminoethyl) methacrylate) (PNIPAM‐co‐PDMA) grafted onto sodium alginate (NaAlg) as a biocompatible polymer and iron oxide nanoparticles (ION) as nanometric base (PND/ION‐NG). This was then added into a solution of PDMA grafted onto NaAlg. Through dropwise addition of mixed aqueous solution of iron salts into the prepared polymeric solution, a novel hydrogel nanocomposite with excellent pH, thermal and magnetic responsivity was fabricated. The synthesized samples were fully characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy with energy‐dispersive X‐ray analysis, vibrating sample magnetometry and atomic force microscopy. A mechanism for the formation of PNIPAM‐co‐PDMA/NaAlg‐ION nanogel–PDMA/NaAlg‐ION hydrogel and PND/ION nanogel is suggested. Swelling capacity was measured at various temperatures (25 to 45 °C), pH values (from 2 to 11) and magnetic field and under load (0.3 psi) and the dependence of swelling properties of the nanogel–hydrogel nanocomposite on these factors was well demonstrated. The release rate of doxorubicin hydrochloride (DOX) as an anticancer drug was studied at different pH values and temperatures in the presence and absence of a magnetic field. The results showed that these factors have a high impact on drug release from this nanocomposite. The result showed that DOX release could be sustained for up to 12.5 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or nanogel alone (<1 day). The results indicated that the nanogel–hydrogel nanocomposite can serve as a novel nanocarrier for anticancer drug delivery. © 2019 Society of Chemical Industry     

Novel thermosensitive hydrogel composites based on poly(d,l‐lactide‐co‐glycolide) nanoparticles embedded in poly(n‐isopropyl acrylamide) with sustained drug‐release behavior

To reach sustained drug release, a new composite drug‐delivery system consisting of poly(d,l ‐lactide‐co‐glycolide) (PLGA) nanoparticles (NPs) embedded in thermosensitive poly(N‐isopropyl acrylamide) (PNIPAAm) hydrogels was developed. The PNIPAAm hydrogels were synthesized by free‐radical polymerization and were crosslinked with poly(ethylene glycol) diacrylate, and the PLGA NPs were prepared by a water‐in‐oil‐in‐water double‐emulsion solvent‐evaporation method. The release behavior of the composite hydrogels loaded with albumin–fluorescein isothiocyanate conjugate was studied and compared with that of the drug‐loaded neat hydrogel and PLGA NPs. The results indicate that we could best control the release rate of the drug by loading it to the PLGA NPs and then embedding the whole system in the PNIPAAm hydrogels. The developed composite hydrogel systems showed near zero‐order drug‐release kinetics along with a reduction or omission of initial burst release. The differential scanning calorimetry results reveal that the lower critical solution temperature of the developed composite systems remained almost unchanged (<1°C increase only). Such a characteristic indicated that the thermosensitivity of the PNIPAAm hydrogel was not distinctively affected by the addition of PLGA NPs. In conclusion, an approach was demonstrated for the successful preparation of a new hybrid hydrogel system having improved drug‐release behavior with retained thermosensitivity. The developed systems have enormous potential for many biotechnological applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40625.     

Preparation a novel pH‐sensitive blend hydrogel based on polyaspartic acid and ethylcellulose for controlled release of naproxen sodium

Hydrogels based on pH‐sensitive polymers are of great interest as potential biomaterials for the controlled delivery of drug molecules. In this study, a novel, pH‐sensitive hydrogel was synthesized by poly(aspartic acid) (PASP) crosslinked with 1,6‐hexanediamine and reinforced with ethylcellulose (EC). The loading and release characteristics of naproxen sodium (NS) were studied. The PASP–EC blend hydrogels had pH‐sensitive characteristics and were strongly dependent on the pH value. The release kinetics for NS from the PASP–EC blend hydrogels and PASP hydrogel were evaluated in simulated gastric fluid (pH = 1.05) and simulated intestinal fluid (pH = 6.8) at 37°C. The results showed that the drug‐loaded hydrogels were resistant to simulated gastric fluid, and hence, they could be useful for oral drug delivery. Compared with the PASP hydrogel, the PASP–EC blend hydrogels showed a lower release rate of NS in the same pH conditions. It was evident that the presence of hydrophobic groups (EC) retarded the release of NS and led to sustained release. The kinetics of NS release from the drug‐loaded hydrogels conformed to the Korsmeyer–Peppas model. The release exponent of the model was 0.7291, which indicated multiple drug release. The PASP–EC blend hydrogels were biodegradable and pH sensitive; there would be a wide range of applications for them in controlled drug‐delivery systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and characterization of a positive thermoresponsive hydrogel for drug loading and release

A positive thermoresponsive hydrogel composed of poly(acrylic acid)‐graft‐β‐cyclodextrin (PAAc‐g‐β‐CD) and polyacrylamide (PAAm) was synthesized with the sequential interpenetrating polymer network (IPN) method for the purpose of improving its loading and release of drugs. The structure and properties of the PAAc‐g‐β‐CD/PAAm hydrogel (IPN hydrogel) were characterized with Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and swelling measurements. FTIR studies showed that the IPN hydrogel was primarily composed of an IPN of PAAc‐g‐β‐CD and PAAm. The data from DSC and swelling measurements indicated that the phase‐transition temperature or upper critical solution temperature (UCST) of the IPN hydrogel was approximately 35°C. Through the measurement of the temperature dependence of the swelling, increases in the UCST and non‐sensitivity to changes in the salt concentration were observed for the IPN hydrogel versus the normal IPN hydrogel poly(acrylic acid)/PAAm (without β‐cyclodextrin). Furthermore, the swelling/deswelling kinetics of the IPN hydrogel also exhibited an improved controllable response rate versus the normal IPN hydrogel. Ibuprofen (IBU) was chosen as the model drug for examining loading and release from the IPN hydrogel. The experimental data proved that the IPN hydrogel provided a positive drug release pattern; the IBU released faster at 37°C than at 25°C, and improved drug loading and controlled release were achieved by the IPN hydrogel versus the normal IPN hydrogel. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Colon‐specific oral delivery of vitamin B2 from poly(acrylamide‐co‐maleic acid) hydrogels: An in vitro study

Hydrogels, composed of poly(acrylamide‐co‐maleic acid) were synthesized and the release of vitamin B₂ from these gels was studied as a function of the pH of the external media, the initial amount of the drug loaded, and the crosslinking ratio in the polymer matrix. The gels containing 3.8 mg of the drug per gram gel exhibit almost zero‐order release behavior in the external media of pH 7.4 over the time interval of more than their half‐life period (t_1/2). The amount of the drug loaded into the hydrogel also affected the dynamic release of the encapsulated drug. As expected, the gels showed a complete swelling‐dependent mechanism, which was further supported by the similar morphology of the swelling and release profiles of the drug‐loaded sample. The hydrophilic nature of the drug riboflavin does not contribute toward the zero‐order release dynamics of the hydrogel system. On the other hand, the swelling osmotic pressure developed between the gels and the external phase, due to loading of the drug by equilibration of the gels in the alkaline drug solution, plays an effective role in governing the swelling and release profiles. Finally, the minimum release of the drug in the swelling media of pH 2.0 and the maximum release with zero‐order kinetics in the medium of pH 7.4 suggest that the proposed drug‐delivery devices have a significant potential to be used as an oral drug‐delivery system for colon‐specific delivery along the gastrointestinal (GI) tract. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1133–1145, 2002; DOI 10.1002/app.10402     

Preparation and in vitro release behavior of urapidil hydrochloride loading into microspheres based on poly(L‐lactide)

Microencapsulation of the antihypertensive drug urapidil hydrochloride was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Poly(L ‐lactide) (PLLA) microspheres were prepared using an alternative oil‐in‐water (O/W) solvent‐evaporation method such as the O/W cosolvent solvent‐evaporation method and O/W with various electrolytes added to the aqueous phase method. The surface morphology and the size of the microspheres were observed by scanning electron microscope. Meanwhile, the drug loading efficiency of microspheres and the in vitro release of urapidil hydrochloride from microspheres were performed. The release study indicated that the urapidil hydrochloride‐PLLA microspheres exhibited better sustained release capacity, and the kinetics of urapidil hydrochloride‐PLLA microspheres in vitro release could be described by the Higuchi equation. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010