An aptamerelectrochemical sensor based on functional carbon nanofibers for tetracycline determination.

Fe-Co@CNF was synthesized by electrospinning technology, and AuNPs was loaded onto Fe-Co@CNF by in-situ reduction to obtain Fe-Co@CNF@AuNPs composite material, which was used as the working electrode based on Au-S bond cooperation. The tetracycline electrochemical sensing interface Fe-Co@CNF@AuNPs@Apt was constructed by connecting mercaptoylated tetracycline (TC) aptamers on Fe-Co@CNF@AuNPs surface. The morphology and composition of Fe-Co@CNF@AuNPs composites were characterized by SEM, TEM, EDS, XRD and XPS, and the electrochemical properties of tetracycline were evaluated by CV and DPV. The results showed that the addition of Fe and Co did not destroy the structure of the original carbon nanofibers, and their synergistic effect enhanced the electrocatalytic performance, effective electrode area and electron transfer ability of carbon nanofibers. AuNPs are evenly distributed over the fibers, which effectively improves the electrical conductivity of the material. Under the optimal conditions, the theoretical detection limit of tetracycline was 0.213 nM, and the linear detection range was 5.12-10 mM, which could successfully detect tetracycline in milk.

Quantitative determination of potential genotoxic impurities in metformin hydrochloride and empagliflozin tablets through ultra-performance liquid chromatographymass spectrometry.

An increasing number of drug research institutions consider genotoxic impurity research a core task in drug research and development. Peroxides in drugs may directly or indirectly attack and damage cell DNA, posing a potential carcinogenic risk to the human body. Currently, the literature only studies hydroperoxide impurities, and benzyl peroxide has not been studied yet. In this study, an effective method for ultra-performance liquid chromatographymass spectrometry (UPLCMS/MS) was established and verified to detect and quantify the potential genotoxic impurity (PGI), empagliflozin benzyl peroxide, in metformin-empagliflozin combination formulations, which has not been reported thus far. A Waters ACQUITY UPLC HSS T3 (3.0 ×100 mm, 1.8 µm) column was used to achieve chromatographic separation with gradient elution. The mass spectrometry conditions were optimized using electrospray ionization in the negative mode. Following the International Conference of Harmonization (ICH) guidelines, this methodology can quantify PGIs at 1.35 ng/mL (5.4 ppm) in samples. This validated method exhibited good linearity over a concentration range of 5.4 to 36 ppm, and the accuracy of this method was in the range of 83.2-95.0% for empagliflozin benzyl peroxide. This approach fills the gap in the detection method for benzyl peroxide impurities in metformin hydrochloride and empagliflozin tablets, providing technical support for the quality control of the drug.

Simultaneous and trace-level quantification of four benzene sulfonate potential genotoxic impurities in doxofylline active pharmaceutical ingredients and tablets using high-performance liquid chromatography with ultraviolet detection.

In the production of doxofylline, the common occurrence of toxic p-toluene sulfonate generation prompted the development and validation of a method using HPLC with ultraviolet detection (HPLC-UV). This method is designed for detecting four potential genotoxic impurities (PGIs) present in both doxofylline drug substance and tablets, with a focus on the UV-absorbing group p-toluene sulfonate. The four impurities were methyl 4-methylbenzenesulfonate (PGI-1), ethyl 4-methylbenzenesulfonate (PGI-2), 2-hydroxyethyl 4-methylbenzenesulfonate (PGI-3), and 2-(4-methylphenyl)sulfonyloxyethyl 4-methylbenzenesulfonate (PGI-4). In this method, chromatographic separation was achieved using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phases consisted of 20% acetonitrile as mobile phase A and pure acetonitrile as mobile phase B, operating in gradient elution mode at a flow rate of 1.0 mL/min. According to the guidelines of the International Conference on Harmonization, it was determined that this method could quantify four PGIs at 0.0225 µg/mL in samples containing 60 mg/mL. The validated approach demonstrated excellent linearity (R2 > 0.999) across the concentration range of 30%-200% (relative to 0.075 µg/mL doxofylline) for the four PGIs. The accuracy of this method for the four PGIs ranged from 94.8% to 100.4%. The reverse-phase-HPLC-UV analytical method developed in this study is characterized by its speed and precision, making it suitable for the sensitive analysis of benzene sulfonate PGIs in doxofylline drug substances and tablets.

Antibody-assisted MIL-53(Fe)/Pt-based electrochemical biosensor for the detection of the nicotine metabolite cotinine.

Antibody-assisted MIL-53(Fe)/Pt was used as an electrochemical biosensor, and a rapid detection method for analysing cotinine content in smokers' saliva was developed based on this sensor. In this sensor, Pt-modified MIL-53(Fe) was modified as an electrode material onto the surface of the working electrode. The amino group was activated with glutaraldehyde and antibodies to cotinine were modified onto the surface and closed with 1% BSA. Cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were used to study the electrode assembly and cotinine detection. The DPV results showed an ideal linear relationship between the current value and the logarithm of the concentration. The detection limit was 0.0092 ng/mL. It has good selectivity and cycling stability. The proposed Abs-MIL-53(Fe)/Pt can effectively and sensitively detect cotinine in saliva and has promisingapplications.

Physicochemical properties and micro-interaction between micro-nanoparticles and anterior corneal multilayer biological interface film for improving drug delivery efficacy: the transformation of tear film turnover mode.

Recently, various novel drug delivery systems have been developed to overcome ocular barriers in order to improve drug efficacy. We have previously reported that montmorillonite (MT) microspheres (MPs) and solid lipid nanoparticles (SLNs) loaded with the anti-glaucoma drug betaxolol hydrochloride (BHC) exhibited sustained drug release and thus intraocular pressure (IOP) lowering effects. Here, we investigated the effect of physicochemical particle parameters on the micro-interactions with tear film mucins and corneal epithelial cells. Results showed that the MT-BHC SLNs and MT-BHC MPs eye drops significantly prolonged the precorneal retention time due to their higher viscosity and lower surface tension and contact angle compared with the BHC solution, with MT-BHC MPs exhibiting the longest retention due to their stronger hydrophobic surface. The cumulative release of MT-BHC SLNs and MT-BHC MPs was up to 87.78% and 80.43% after 12 h, respectively. Tear elimination pharmacokinetics study further confirmed that the prolonged precorneal retention time of the formulations was due to the micro-interaction between the positively charged formulations and the negatively charged tear film mucins. Moreover, the area under the IOP reduction curve (AUC) of MT-BHC SLNs and MT-BHC MPs was 1.4 and 2.5 times that of the BHC solution. Accordingly, the MT-BHC MPs also exhibit the most consistent and long-lasting IOP-lowering effect. Ocular irritation experiments showed no significant toxicity of either. Taken together, MT MPs may have the potential for more effective glaucoma treatment.

Desonide Nanoemulsion Gel for Transdermal Absorption Drug Delivery: Pharmacodynamic and Safety Evaluation.

BACKGROUND: When administered transdermally, desonide is ineffective due to its poor solubility. As a new transdermal delivery system, nanoemulsion gel has demonstrated significant advantages for drug delivery over conventional formulations. We have established desonide nanoemulsion gel (DES NE gel) for better transdermal absorption, but its efficacy and safety still need to be evaluated. This study aims to provide additional evidence demonstrating the improved pharmacodynamics and safety of transdermal delivery of Desonide via nanoemulsion gel. METHODS: Pharmacodynamics and safety of Desonide nanoemulsion gel were evaluated using Desonate ® as the reference formulation. To assess the difference in curative effect between DES NE gel and Desonate® and to ensure safety, atopic dermatitis (AD) models in KM mice were developed using 2,4-dinitrofluorobenzene (DNFB). The degree of ear swelling, ear mass difference, thymus, spleen index, and HE conventional pathology of mice were used as pharmacodynamic evaluation indexes, and the irritation was predicted by the New Zealand rabbit epidermal stimulation assay. RESULTS: Nanoemulsion gels may facilitate transdermal penetration of drugs by influencing the skin condition. Medium and high doses of DES NE gel significantly ameliorated the inflammation and swelling of the ear caused by dermatitis/eczema in mice. In addition, compared with DES gel, skin irritation extent did not increase. CONCLUSION: Nanoemulsion gel can be applied to improve the efficacy of drugs with low potency or poor solubility. DES NE gel provides a higher transdermal potential than other delivery systems. In this study, it was found that nanoemulsion gel is a promising percutaneous carrier of DES. DES NE-GEL has a significant curative effect on dermatitis/eczema in a mouse model and is expected to provide a new, efficient, and low toxic preparation for clinical treatment of dermatitis/eczema through the percutaneous system.

Critical Evaluation of Multifunctional Betaxolol Hydrochloride Nanoformulations for Effective Sustained Intraocular Pressure Reduction.

Introduction: Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability. Methods: We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface. Results: The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy. Conclusion: The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.

Surface Plasmon Resonance (SPR) biosensor for detection of mycotoxins: A review.

Mycotoxin is one of the most important natural pollutants, which poses a global threat to food safety. However, the pollution of mold in food production is inevitable. The detection technology of mycotoxins in food production is an important means to prevent the damage of mycotoxins, so rapid detection and screening to avoid pollution diffusion is essential. The focus of this review is to update the literature on the detection of mycotoxins by surface plasmon resonance (SPR) technology, rather than just traditional chromatographic methods. As a relatively novel and simple analytical method, SPR has been proved to be fast, sensitive and label-free, and has been widely used in real-time qualitative and quantitative analysis of various pollutants. This paper aims to give a broad overview of the sensors for detection and analysis of several common mycotoxins.

Application of the Non-dominated Sorting Genetic Algorithm II in Multi-objective Optimization of Orally Disintegrating Tablet Formulation.

In the context of increasing application of modelling methods in the field of pharmaceutics, this study aims to reduce the weight of sildenafil orally disintegrating tablets (ODTs) and optimize their formulation through modelling methods. To achieve the goal, the back-propagation neural network (BPNN)-based non-dominated sorting genetic algorithm II (NSGA-II) was introduced to establish the models and to optimize the percentage of magnesium stearate (MgSt), crospovidone (PVPP), and croscarmellose sodium (CCNa) to obtain satisfactory candidate ODTs. Ultimately, the bioequivalence trial was conducted to verify the effectiveness of the formulation. With the support of the neural network, the model showed satisfactory results in the prediction of hardness and disintegration time of ODTs, and the pareto front obtained by the NSGA-II suggested that there was a strong "competition" between disintegration time and hardness. Since disintegration time should be given the priority, the optimal formulation was determined as 1% MgSt, 6% CCNa, and 2.6% PVPP. The bioequivalence trial results indicated a bioequivalence between the test and the reference formulations of sildenafil, and better medication experience for the test formulation. A bioequivalent formulation with better medication experience is successfully prepared using the NSGA-II. It proves that the NSGA-II is applicable to multi-objective optimization of the drug formulation.

Mesoporous NiO@ZnO nanofiber membranes via single-nozzle electrospinning for urine metabolism analysis of smokers.

An effective matrix is very important for impact laser desorption/ionization mass spectrometry (LDI-MS), and the physicochemical properties of the matrix nanostructures can impact the LDI-MS performance. In this study, a simple and efficient single-nozzle electrospinning strategy using polystyrene (PS) spheres and polyvinyl pyrrolidone (PVP) to construct a mesoporous NiO@ZnO nanofiber membrane was developed. Compared with the NiO and ZnO nanomaterials alone, the obtained NiO@ZnO nanofiber membrane was proven to be an efficient material as the matrix to increase the intensity of the mass spectrum speaks of small molecules. The NiO@ZnO nanofiber membrane was used as the matrix for the LDI-MS method for the urine metabolism analysis of smokers, which revealed differences in the metabolic and the possible metabolic markers of smokers through the statistical analysis of the urine samples of 27 smokers and 11 nonsmoker controls.

Simultaneous and trace level quantification of two potential genotoxic impurities in valsartan drug substance using UPLC-MS/MS.

A sensitive and selective Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for the identification and quantification of two potential genotoxic impurities (PGIs) - viz. methyl N-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-N-nitroso-L-valinate (PGI-1) and N-nitroso Valsartan (PGI-2) - in the angiotensin II receptor blocker valsartan. Among these impurities, PGI-1 is a distinctive compound which has never been reported. For this, chromatographic separation was performed using a Waters XBridge BEH C18 column (150 mm × 4.6 mm, 2.5 µm), with ammonium acetate aqueous solution (0.01 mol/L) as mobile phase A and acetonitrile as mobile phase B, in a gradient elution mode at a 0.5 mL/min flow rate. Mass spectrometric conditions were optimized using electrospray ionization (ESI) in positive mode. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying 2 PGIs at 0.016 ppm in samples at 50 mg/mL concentration. This validated approach presented good linearity over the concentration range of 0.016-0.06 ppm for 2 PGIs. The correlation coefficient of each impurity was observed greater than 0.999. The accuracy of this method was in the range of 83-113% for the aforementioned PGIs. In addition, expert knowledge rules (Derek-based) and statistical (Q) SAR evaluation system (Sarah-based) were used to evaluate and classify the genotoxicity of both valsartan-related PGIs as well as to define their standard limits. The predicted results were positive and classified into the third category, and the total nitrosamine limit was set to 0.03 ppm. As such, this approach represents a good quality control system for the simultaneous and precise quantitation of PGIs in valsartan.

Pharmacokinetics and food impact assessment of ademetionine enteric-coated tablet as an endogenous substance drug in healthy Chinese volunteers.

WHAT IS KNOWN AND OBJECTIVES: Ademetionine 1,4-Butanedisulfonate (SAMe) enteric-coated tablets are widely used for treatment of pre-cirrhotic and cirrhotic intrahepatic cholestasis, as well as intrahepatic cholestasis of pregnancy (ICP), but incomplete clinical data and interference from endogenous substances pose numerous challenges for clinical trial of ademetionine. The objective of this study was to evaluate the pharmacokinetic profile of SAMe enteric-coated tablets and to assess its food impact and safety in healthy Chinese subjects. METHODS: A randomized, open-label, single-dose study was carried out to determine the pharmacokinetics of SAMe enteric-coated tablets administered in both fasted and postprandial conditions. Baseline collection and data adjustment were required to reduce the effect of endogenous substances. Relevant pharmacokinetic data from subjects administered the reference formulation will be disclosed and utilized in this thesis. RESULTS: Twenty-four subjects with a body mass index (BMI) of 19-24 kg/m2 were enrolled in the study and all completed the trial. The impact of food on the drug was noticeable, with faster absorption in the fasting group (Tmax , 4.50 ± 1.07 and 7.50 ± 1.58 for the fasting and postprandial groups, respectively) but higher exposure in the postprandial group (AUC0-inf , 4021.02 ± 3377.13 and 5087.28 ± 3539.26 for the fasting and postprandial groups, respectively). No serious adverse effects were observed in the fasted and postprandial conditions. WHAT IS NEW AND CONCLUSIONS: The pharmacokinetic profile of SAMe enteric-coated tablets in healthy Chinese subjects was partially complemented in this study. SAMe enteric-coated tablets showed promising safety in fasted and postprandial conditions. However, the impact of food on the drug was significant and might access to the absorption site and affect biochemical reactions.

Wettability and contact angle affect precorneal retention and pharmacodynamic behavior of microspheres.

In the present study, we describe the development of betaxolol hydrochloride and montmorillonite with ion exchange in a single formulation to create a novel micro-interactive dual-functioning sustained-release delivery system (MIDFDS) for the treatment of glaucoma. Betaxolol hydrochloride molecule was loaded onto the montmorillonite by ion exchange and MIDFDS formation was confirmed by XPS data. MIDFDS showed similar physicochemical properties to those of Betoptic, such as particle size, pH, osmotic pressure, and rheological properties. Nevertheless, the microdialysis and intraocular pressure test revealed better in vivo performance of MIDFDS, such as pharmacokinetics and pharmacodynamics. With regards to wettability, MIDFDS had a larger contact angle (54.66 ± 5.35°) than Betoptic (36.68 ± 1.77°), enabling the MIDFDS (2.93 s) to spread slower on the cornea than Betoptic (2.50 s). Moderate spreading behavior and oppositely charged electrostatic micro-interactions had a comprehensive influence on micro-interactions with the tear film residue, resulting in a longer precorneal retention time. Furthermore, MIDFDS had a significant sustained-release effect, with complete release near the cornea. The dual-functioning sustained-release carrier together with prolonged pre-corneal retention time (80 min) provided sufficiently high drug concentrations in the aqueous humor to achieve a more stable and long-term IOP reduction for 10 h. In addition, cytotoxicity and hemolysis tests showed that MIDFDS had better biocompatibility than Betoptic. The dual-functioning microspheres presented in this study provide the possibility for improved compliance due to low cytotoxicity and hemolysis, which suggests promising clinical implications.

The Role of Cyclophilins in Inflammatory Bowel Disease and Colorectal Cancer.

Cyclophilins (Cyps) is a kind of ubiquitous protein family in organisms, which has biological functions such as promoting intracellular protein folding and participating in the pathological processes of inflammation and tumor. Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are two common intestinal diseases, but the etiology and pathogenesis of these two diseases are still unclear. IBD and CRC are closely associated, IBD has always been considered as one of the main risks of CRC. However, the role of Cyps in these two related intestinal diseases is rarely studied and reported. In this review, the expression of CypA, CypB and CypD in IBD, especially ulcerative colitis (UC), and CRC, their relationship with the development of these two intestinal diseases, as well as the possible pathogenesis, were briefly summarized, so as to provide modest reference for clinical researches and treatments in future.

Nanoemulgel for Improved Topical Delivery of Desonide: Formulation Design and Characterization.

This research aimed to develop a novel drug delivery system to improve treatment of skin disorders. The system is comprised of a Carbopol 980-based nanoemulgel (NE-gel) containing a desonide (DES; 0.05%, w/w) nanoemulsion (NE), which has a small particle size, high encapsulation efficiency, good thermodynamic stability, good permeation ability, and high skin retention. DES-loaded NE (DES-NE) was prepared by high-pressure homogenization. The developed formulation was characterized by differential scanning calorimetry (DSC), X-ray diffraction, drug release, skin permeation, and drug retention. DES in vitro release and skin permeation studies with different formulations of artificial membrane and rat abdominal skin were performed with the Franz diffusion cell system. Confocal laser scanning microscopy (CLSM) was used to detect the localization and permeation pathways of drugs in the skin. Compared with commercially available gel (CA-gel) and NE, the NE-gel release process conformed to the Higuchi release model (R2 = 0.9813). NE-gel prolonged the drug release time and allowed for reduced administration dose and frequency. The unit cumulative permeation of NE and NE-gel through the skin for 12 h was 63.13 ± 2.78 and 42.53 ± 2.06 µg/cm2, respectively, values significantly higher (p < 0.01) than that of the CA-gel (30.65 ± 1.25 µg/cm2) and CA-cream (15.21 ± 0.97 µg/cm2). The DES-NE and DES NE-gel skin drug retention was significantly higher than commercially available formulations (p < 0.01). Hence, the prepared NE-gel is a potential vehicle for improved topical DES delivery for better treatment of skin disorders.

Preparation and characterization of bupivacaine multivesicular liposome: A QbD study about the effects of formulation and process on critical quality attributes.

This study extends QbD principles to liposomal products containing a hydrophilic active pharmaceutical ingredient (API). The feasibility and advantages of the QbD concept for multivesicular liposome-based systems were demonstrated. We selected the local anesthetic drug bupivacaine as a model compound. Desired properties for three critical attributes of multivesicular liposome drug products, namely, the particle size, morphology, and drug encapsulation efficiency, were defined and evaluated. The liposome preparation process significantly affected both the liposome particle size and drug encapsulation efficiency. In this study, the effects of material attributes and processing parameters during the preparation of liposomes were studied in detail using a microscope and particle size analyzer. We used risk assessment to monitor several factors that substantially affect the encapsulation rate and particle size.

The synthesis of Zr-metal-organic framework functionalized magnetic graphene nanocomposites as an adsorbent for fast determination of multi-pesticide residues in tobacco samples.

In this paper, a simple and reliable method has been established to determine the residues of nine pesticides in tobacco by using GC-MS coupled with magnetic solid phase extraction. A novel magnetic Zr-MOF nanocomposite based on graphene was synthesized, and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy and N2 adsorption-desorption measurements. The prepared material has the advantage of large surface area (178 m2/g), good magnetic response and high thermal stability, which is shown to be suited for the fast enrichment of multi-pesticides in tobacco matrix. The extraction conditions including amount of adsorbent, adsorption time, eluting solvent as well as desorption time were investigated. The whole process of pretreatment is accomplished within 10 min. This method shows low limit of detection, wide linear range and good reproducibility (relative standard deviations <12.7%), satisfactory recoveries were obtained, ranging from 57.9% to 126.3% for tobacco samples.

Metabolomic profiling of rat urine after oral administration of the prescription antipyretic Hao Jia Xu Re Qing Granules by UPLC/Q-TOF-MS.

Hao Jia Xu Re Qing Granules (HJ), is an effective clinically used antipyretic based on traditional Chinese medicine. Although its antipyretic therapeutic effectiveness is obvious, its therapeutic mechanism has not been comprehensively explored yet. In this research, we first identified potential biomarkers which may be relevant for the antipyretic effect of HJ based on urine metabolomics using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A rat model of fever was established using the yeast-induced febrile response. Total-ion-current metabolic profiles of different groups were acquired and the data were processed by multivariate statistical analysis-partial least-squares discriminant analysis. As envisioned, the results revealed changes of urine metabolites related to the antipyretic effect. Fourteen potential biomarkers were selected from the urine samples based on the results of Student's t-test, "shrinkage t", variable importance in projection and partial least-squares discriminant analysis. N-Acetylleucine, kynurenic acid, indole-3-ethanol, nicotinuric acid, pantothenic acid and tryptophan were the most significant biomarkers found in the urine samples, and may be crucially related to the antipyretic effect of HJ. Consequently, we propose the hypothesis that the significant antipyretic effect the HJ may be related to the inhibition of tryptophan metabolism. This research thus provides strong theoretical support and further direction to explain the antipyretic mechanism of HJ, laying the foundation for future studies.

Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug.

The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH 6.8 and pH 1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24 h in acidic media (pH 1.2). The release profile in acidic media was similar to the alkaline media (pH 6.8) with a similarity factor (f2) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile.