Pharmaceutical Sciences News

Win an iPad with Elsevier Mobile Application Competition

2012-04-19T12:00:00Z

Could your idea help authors to submit their papers while they are on the move? Or perhaps you have an idea for an application that involves several journals in a subject area? Whatever your journal app ideas, submit your suggestions to Elsevier’s Best Mobile App Competition today! You don’t have to be a Techie, you just need to have good ideas! Put your pen to paper (or fingers to keyboard) and write these ideas down. Who knows? You might even win an iPad for your efforts! Submit your idea before 31 May 2012! http://elsevierauthormobileapp.com/

BIGGERBRAINS on Networking in your Research Career

2012-03-27T12:00:00Z

Interview with Prof Aldo Boccaccini. Department of Materials Science and Engineering University of Erlangen-Nuremberg, Germany, and Editor-in-Chief of Materials Letters. Interview focuses on the importance of networking in the early stages of your career.

BIGGERBRAINS: Publishing and Career Advice to Young, Ambitious Scientists

2012-03-23T12:00:00Z

Video interview with Dr. Guido Kroemer. Professor at the Faculty of Medicine of the University of Paris Descartes, and Editor-in-Chief of Biochemical and Biophysical Research Communications journal (BBRC).

Elsevier’s Direct2Experts

2012-03-21T12:00:00Z

Find potential collaborators who conduct related research in a variety of expertise areas with Elsevier’s Direct2Experts.

Charting a Course for a Successful Research Career

2012-03-20T12:00:00Z

Charting a Course for a Successful Research Career is a crash course of practical advice on how to plan your career.

Synthesis and evaluation of biotin-conjugated pH-responsive polymeric micelles as drug carriers [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Ji Hyun Kim, Yi Li, Min Sang Kim, Seong Woo Kang, Ji Hoon Jeong, Doo Sung Lee
pH-Responsive polymeric micelles have been investigated as drug carriers for chemotherapy. Ligand-mediated polymeric micelles, which can penetrate the target tumors due to their high binding affinity to a specific receptor on the surface of tumors, were developed to achieve targeted drug delivery. In this study, biotin-conjugated methoxypoly(ethylene glycol)-grafted-poly(β-amino ester) was prepared for active and pH-sensitive tumor targeting. These polymers were modified by cholesteryl chloroformate to improve the hydrophobicity of the micelle core. The structure of the biotin-conjugated polymer was confirmed by ¹H NMR spectroscopy, and the existence of biotin at the surface of the polymeric micelles was evaluated by an 4′-hydroxyazobenzene-2-carboxylic acid/avidin (HABA/avidin) binding assay at different pHs. The micelle properties were determined by dynamic light scattering and the result showed that the mean size of the polymeric micelles was approximately 20 nm. For cancer therapy, doxorubicin (DOX) was loaded into the polymeric micelles with a high loading efficiency. From the in vitro cellular uptake results, the biotin-conjugated polymeric micelles can effectively release doxorubicin at acidic tumor cells compared to the micelles without biotin. Overall, biotin-conjugated pH-responsive polymeric micelles have great potential to be used as drug carriers.

Graphical Abstract

Chitosan-based luminescent/magnetic hybrid nanogels for insulin delivery, cell imaging, and antidiabetic research of dietary supplements [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Jian-Min Shen, Luan Xu, Yan Lu, Hui-Ming Cao, Zhi-Gang Xu, Tong Chen, Hai-Xia Zhang
In this work, the chitosan-based luminescent/magnetic (CLM) nanomaterials were synthesized by direct gelation of chitosan, CdTe and superparamagnetic iron oxide into the hybrid nanogels. The morphology, sizes and properties of the nanogels prepared with different chitosan/QD/MNP ratios and under different processing parameters were researched. Fluorescence microscopy, FTIR spectra and TEM images confirmed the success of the preparation of the CLM hybrid nanogels. Spherical CLM hybrid nanogels with appropriate average sizes (<160 nm) were used for insulin loading. The actual loading amount of insulin was approximately 40.1 mg/g. Human normal hepatocytes L02 cell line was used to explore the effects of additives, such as mangiferin (MF), (−)-epigallocatechin gallate (EGCG), and (−)-epicatechin gallate (ECG) on the insulin-receptor-mediated cellular uptake using insulin-loaded CLM (ICLM) hybrid nanogels. Above 80% of viability of L02 cells were watched at a nanogels concentration of 500 μg/mL whatever the additives existed or not. The study discovered that the fluorescent signals of the ICLM hybrid nanogels in L02 cells were more intense in the presence of MF, EGCG and ECG in medium than in the absence of these components, respectively. These results demonstrate that MF, EGCG and ECG are potentially able to enhance targeting combination of insulin with L02 cells and improve insulin sensitivity in L02 cells. The hybrid nanogels designed as a targeting carrier can potentially offer an approach for integration of insulin delivery, cell imaging, and antidiabetic investigation of dietary supplements.

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Investigation of an active film coating to prepare new fixed-dose combination tablets for treatment of diabetes [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Ju-Young Kim, Dong-Wook Kim, Yun-Mo Kuk, Chun-Woong Park, Yun-Seok Rhee, Tack-Oon Oh, Kwon-Yeon Weon, Eun-Seok Park
The aim of the present study was to formulate new fixed-dose combination tablets (FCTs) by coating a glimepiride (GLM) immediate-release (IR) layer on a metformin hydrochloride (MTF) extended-release (ER) core tablet using perforated film coating equipment. Composition of GLM-IR coating suspension for homogeneity was studied and application of near-infrared spectroscopy (NIR) to determine the end-point of the coating process was also investigated. The final product was administered to healthy male volunteers and its pharmacokinetic parameters were analyzed. GLM-IR coating suspension was prepared with a ratio of SLS to GLM at 0.75 for homogeneity. An inert mid-layer was introduced to prevent contact between MTF-ER core tablet and GLM-IR layer, which led to an increased release rate of GLM in pH 7.8 medium. The proportional correlation was confirmed between analytical results of GLM determined by NIRS and those by HPLC-UV. Thus, the end-point of the GLM coating process was determined by NIRS, the fast and non-destructive method. New FCTs were confirmed to be bioequivalent to the marketed product.

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An insight into the role of barrier related skin proteins [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Kiyomi Wato, Takuya Hara, Kenjirou Yamana, Hiroshi Nakao, Toshio Inagi, Katsuhide Terada
It is well-known that intercellular lipids in the stratum corneum (SC) of the skin play an important role in maintaining barrier function, and many types of penetration enhancers affecting lipids are used in topical products to improve transdermal drug permeability. Recently, it was reported that functional proteins in tight junctions of the epidermis are important for barrier function. In this study, the effects of penetration enhancers such as fatty esters, amines/amides, and alcohols on the barrier function of the skin were evaluated in rat skin and normal human-derived epidermal keratinocytes (NHEK). All penetration enhancers decreased the electrical impedance (EI), however, the potencies of some penetration enhancers were not equal between rat skin and NHEK. The differences were clarified by immunohistochemical studies: some fatty esters decreased the immunoreactivity of involucrin and keratin 10 in the upper layer of the epidermis, while alcohols decreased the immunoreactivity of desmoglein-1, claudin-1, and E-cadherin located in the lower layer of the epidermis. From these results, it is suggested that penetration enhancers show new action mechanisms disturbing barrier-related proteins in epidermis, which are classified into two categories depending on their action sites.

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Structural evaluation of probucol nanoparticles in water by atomic force microscopy [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Kunikazu Moribe, Waree Limwikrant, Kenjirou Higashi, Keiji Yamamoto
Structural evaluation of probucol nanoparticles coground with polyvinylpyrrolidone K17 and sodium dodecyl sulfate for 90 min was performed by solid-state nuclear magnetic resonance (NMR) spectroscopy and atomic force microscopy (AFM) with force–distance curve analysis. The results of solid-state NMR indicated that the cogrinding changed crystalline probucol to amorphous form. The number-averaged mean heights of probucol particles in the ground mixture (GM) suspension were determined by AFM to be 6 and 15 nm for freshly prepared and 24 h-stored samples, respectively. Nucleation and the subsequent crystal growth might have occurred after the GM was dispersed in water. The presence of probucol nanocrystals and agglomeration of the primary probucol nanoparticles were recognized by AFM force–distance curve analysis. AFM could be a promising tool to evaluate the structure of nanoparticles as well as their agglomeration behavior in aqueous media.

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Modeling dispersion of dry powders for inhalation. The concepts of total fines, cohesive energy and interaction parameters [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Kyrre Thalberg, Elna Berg, Magnus Fransson
A range of carrier based dry powder formulations consisting of micronized drug, carrier lactose and, in some formulations, lactose fines were produced and tested for dispersibility, i.e. fine particle fraction (FPF). Two different drugs were used, budesonide (BUD) and beclomethasone dipropionate (BDP). A model based on the total amount of fines (TF) and the cohesive energy (CE) of the formulation is proposed, where TF is the sum of added drug, lactose fines and the fines inherent to the carrier. The expression for CE is derived from regular solutions theory and allows calculation of interparticle interaction parameters. The model was able to describe experimental data well, such as the decrease in FPF when the proportion of drug is increased at a constant TF level and the non-linear effects seen when a cohesive drug is added to carrier. BDP and BUD were found to be 5.3 times and 1.8 times more cohesive than lactose fines respectively. The model hence provides a link between the macroscopic behavior of a dry powder formulation and the interaction between the different species at the particulate level.

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Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Lexi Wang, Aiping Wang, Xiaolei Zhao, Ximing Liu, Dan Wang, Fengying Sun, Youxin Li
Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution–gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application.

Graphical Abstract

A novel liposome-encapsulated hemoglobin/silica nanoparticle as an oxygen carrier [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Mingxian Liu, Lihua Gan, Liuhua Chen, Dazhang Zhu, Zijie Xu, Zhixian Hao, Longwu Chen
A novel liposome-encapsulated hemoglobin/silica nanoparticle (LEHSN) was fabricated by a water-in-oil-in-water (W/O/W) double emulsion approach. Bovine hemoglobin (Hb) was first adsorbed onto the surfaces of silica nanoparticles (SNs), and then the complex of Hb/SNs was encapsulated by liposome to form LEHSN which has a core–shell supramolecular structure. On the one hand, liposomes built a cell membrane-like environment for the controlled release of Hb. On the other hand, SNs which act as rigid core provide a supported framework for lecithin membrane, and enhance the stability of liposomes. In comparison with liposome-encapsulated Hb (LEH), LEHSN shows substantially enhanced stability and improved release property of Hb in vitro. This study highlights the potential of the novel LEHSN as an oxygen carrier for pharmaceutical applications.

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Sterilization stability of vesicular phospholipid gels loaded with cytarabine for brain implant [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Na Qi, Xing Tang, Xia Lin, Pengfei Gu, Cuifang Cai, Hui Xu, Haibing He, Yu Zhang
The aim of this study was to investigate the sterilization stability of cytarabine (Ara-C) loaded vesicular phospholipid gels (VPGs). VPGs were prepared by high pressure homogenization method intended for the treatment of glioblastoma multiforme (GBM) in brain as injectable implant. The particle size of VPGs after redispersion was 119.6 ± 66.24 nm, and entrapment efficiency (EE) was 32.6 ± 2.1%. Drug release in vitro from VPGs sustained for 80 h with 48.1% initial release within 1 h, and rheological studies demonstrated a gel-like behavior. Comparatively, after autoclaved sterilization, increased particle size and EE were obtained as 165.6 ± 71.89 nm and 62.6 ± 2.3%, respectively. Additionally, characteristics of drug release were significantly altered with obviously prolonged release time to 450 h and remarkable reduced initial release to 24.7%. Also, the viscoelasticity was reinforced with clearly decreased fluidity. This result could be explained by the fusion of small vesicles witnessed in TEM observation, which resulted in percentages change of vesicle groups with different size. However, reduced Ara-C and increased lysophosphatidylcholine (LPC) were observed. Among the stabilizers, addition of sodium sulfite showed best effects with high stability of Ara-C and phospholipids. This may be explained by the presence of SO 3 ⁻ , free radicals produced by sodium sulfite. Being an hydroxyl radical scavenger, it can reduce the generation of HO free radicals. These results show that, with addition of appropriate stabilizers, VPGs can be autoclaved with high stability, and it is a promising dosage form for treatment of GBM after injection into resectable or nonresectable neoplasms with sustained release properties.

Graphical Abstract

Lysozyme-loaded, electrospun chitosan-based nanofiber mats for wound healing [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Natthan Charernsriwilaiwat, Praneet Opanasopit, Theerasak Rojanarata, Tanasait Ngawhirunpat
In this study, a blend mixture of chitosan–ethylenediaminetetraacetic acid (CS 2 wt%–EDTA) at a weight ratio of 30/70 and polyvinyl alcohol (PVA) solution (10 wt%) was electrospun to produce fibrous mats with lysozyme (10, 20 and 30 wt%) used for wound healing. The morphology and diameter of the electrospun fiber mats with and without lysozyme were analyzed by scanning electron microscopy (SEM). The amount of lysozyme loaded in the nanofiber mats was measured by HPLC. The cell lysis activity of the lysozyme was investigated with Micrococcus lysodeikticus cells as a substrate. The wound healing activity was performed in vivo using male Wistar rats. The SEM images of all lysozyme-loaded fibers show a smooth fiber without beads with an average diameter of 143–209 nm. The amount of lysozyme loaded in the nanofiber mats was slightly decreased when the initial concentration of lysozyme was increased. The rapid lysozyme release from the nanofiber mats was obtained and is dependent on the lysozyme-loading amount. In animal wound healing, lysozyme loaded CS–EDTA nanofiber mats accelerated the rate of wound healing when compared to the controls (gauze). In conclusion, our experiments demonstrated that biomaterials composed of lysozyme loaded CS–EDTA nanofibers have a potential for wound healing.

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Elastic–plastic contact law for simulation of tablet crushing using the biharmonic equation [International Journal of Pharmaceutics–plastic contact law for simulation of tablet crushing using the biharmonic equation]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Norhayati Ahmat, Hassan Ugail, Gabriela González Castro
This work presents a technique for shape modelling of cylindrical and spherical tablets subject to compression. This technique is based on the use of partial differential equations (PDEs), the biharmonic equation in particular. The deformation of the compressed elastic–plastic tablet of both shapes was obtained using the existing contact models found in literature. The mathematical properties of the biharmonic equation have been exploited to achieve simple mathematical expressions characterising the shape of the distorted tablet. Thus, the height, radius and contact area of both configurations due to uniaxial compression are represented by analytic expressions relating the coefficients associated with the solution of the biharmonic equation. The results obtained from the PDE-based simulation are compared with the theoretical ones. It is found that the analytic solution of the elliptic PDE can be utilised to represent the physical changes of the deformed object.

Graphical Abstract

Physico-chemical characteristics of methotrexate-entrapped oleic acid-containing deformable liposomes for in vitro transepidermal delivery targeting psoriasis treatment [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Pathomthat Srisuk, Phensri Thongnopnua, Uracha Raktanonchai, Sorada Kanokpanont
This study aimed to investigate the physico-chemical characteristics and in vitro permeability of methotrexate (MTX)-entrapped deformable liposomes prepared from phosphatidylcholine (PC) and oleic acid (OA), comparing with those of MTX-entrapped conventional liposomes prepared from PC and cholesterol (CH). Two formulations of MTX-entrapped PC2:CH1 and PC9:CH1 liposomes and one formulation of MTX-entrapped PC2.5:OA1 liposomes were prepared. The size, size distribution, zeta potential, thermal properties, entrapment efficiency, stability, and in vitro permeability across a porcine skin of the MTX-entrapped liposomes were evaluated. All liposome formulations showed a narrow size distribution with the size range of 80–140 nm which is appropriate for the skin permeability. The percentage of MTX loading, entrapment efficiency and the stability of MTX-entrapped PC2:CH1 and PC9:CH1 liposomes were slightly higher than those of MTX-entrapped PC2.5:OA1 liposomes. However, the MTX-entrapped PC2.5:OA1 liposomes enhanced the skin permeability characterized by the higher concentration and flux of MTX diffused across or accumulated in the epidermis and dermis layers of porcine skin. The enhanced permeability of MTX-entrapped PC2.5:OA1 liposomes was explained by 2 mechanisms: (1) the deformable and elasticity characteristics of OA-containing liposomes and (2) a property as a skin penetration enhancer of OA. This suggested that the PC2.5:OA1 deformable liposome was one of promising candidates to enhance the permeability of MTX for the treatment of psoriasis.

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Relationship between dissolution and bioavailability for nimodipine colloidal dispersions: The critical size in improving bioavailability [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Qiang Fu, Longfa Kou, Cheng Gong, Mo Li, Jin Sun, Dong Zhang, Meina Liu, Xiaofan Sui, Kai Liu, Siling Wang, Zhonggui He
To compare the dissolution and bioavailability for nimodipine microcrystals and nanocrystals, and to determine the critical size range in improving the oral absorption of nimodipine. Nimodipine microcrystals and nanocrystals were prepared using a microprecipitation method. The particle size was determined with a laser diffraction method. X-ray powder diffraction was applied to inspect the potential crystal form transition. The aqueous solubility was determined by shaking flasks, and the dissolution behavior was evaluated using the paddle method. The pharmacokinetics was performed in beagle dogs in a crossover experimental design. Three nimodipine colloidal dispersions (16296.7, 4060.0 and 833.3 nm) were prepared, respectively. Nimodipine had undergone crystal form transition during microprecipitation process, but experienced no conversion under the high-pressure homogenization. The colloidal dispersions did not show any difference in aqueous equilibrium solubility. Additionally, the three formulations also displayed similar dissolution curves in purified water and 0.05% SDS. The AUC for dispersions of 4060.0 and 833.3 nm sizes was 1.69 and 2.59-fold higher than that for 16296.7 nm system in dogs. To sum up, the critical particle size was found to be within the range of 833.3–4060.0 nm (average volume-weighted particle size) in improving the bioavailability of nimodipine, and dissolution performance was not an effective index in evaluating the bioavailability for nimodipine colloidal dispersions.

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Colonic luminal surface retention of meloxicam microsponges delivered by erosion based colon-targeted matrix tablet [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Rishabh Srivastava, Deepesh Kumar, Kamla Pathak
The work was aimed at developing calcium-pectinate matrix tablet for colon-targeted delivery of meloxicam (MLX) microsponges. Modified quassi-emulsion solvent diffusion method was used to formulate microsponges (MS), based on 3² full factorial design. The effects of volume of dichloromethane and EudragitRS100 content (independent variables) were determined on the particle size, entrapment efficiency and %cumulative drug release of MS1–MS9. The optimized formulation, MS5 ( d mean = 44.47 μm, %EE = 98.73, %CDR = 97.32 and followed zero order release) was developed into colon-targeted matrix tablet using calcium pectinate as the matrix. The optimized colon-targeted tablet (MS5T2) shielded MLX loaded microsponges in gastrointestinal region and selectively delivered them to colon, as vizualized by vivo fluoroscopy in rabbits. The pharmacokinetic evaluation of MS5T2 in rabbits, revealed appearance of drug appeared in plasma after a lag time of 7 h; a t max of 30 h with Fr = 61.047%, thus presenting a formulation suitable for targeted colonic delivery. CLSM studies provided an evidence for colonic luminal retentive ability of microsponges at the end of 8 h upon oral administration of MS5T2. Thus calcium pectinate matrix tablet loaded with MLX microsponges was developed as a promising system for the colon-specific delivery that has potential for use as an adjuvant therapy for colorectal cancer.

Graphical Abstract

A mathematical model for pulsatile release: Controlled release of rhodamine B from UV-crosslinked thermoresponsive thin films [International Journal of Pharmaceutics]

2012-04-01T12:00:00Z

Publication year: 2012
Source:International Journal of Pharmaceutics, Volume 427, Issue 2
Rongbing Yang, Tuoi Vo T. N., Alexander V. Gorelov, Fawaz Aldabbagh, William M. Carroll, Martin G. Meere, Yury Rochev
A controlled drug delivery system fabricated from a thermoresponsive polymer was designed to obtain a pulsatile release profile which was triggered by altering the temperature of the dissolution medium. Two stages of release behaviour were found: fast release for a swollen state and slow (yet significant and non-negligible) release for a collapsed state. Six cycles of pulsatile release between 4 °C and 40 °C were obtained. The dosage of drug (rhodamine B) released in these cycles could be controlled to deliver approximately equal doses by altering the release time in the swollen state. However, for the first cycle, the swollen release rate was found to be large, and the release time could not be made short enough to prevent a larger dose than desired being delivered. A model was developed based on Fick's law which describes pulsatile release mathematically for the first time, and diffusion coefficients at different temperatures (including temperatures corresponding to both the fully swollen and collapsed states) were estimated by fitting the experimental data with the theoretical release profile given by this model. The effect of temperature on the diffusion coefficient was studied and it was found that in the range of the lower critical solution temperature (LCST), the diffusion coefficient increased with decreasing temperature. The model predicts that the effective lifetime of the system lies in the approximate range of 1–42 h (95% of drug released), depending on how long the system was kept at low temperature (below the LCST). Therefore this system can be used to obtain a controllable pulsatile release profile for small molecule drugs thereby enabling optimum therapeutic effects.