Sustained-release Products Research Articles

Clinical outcomes associated with orphenadrine deliberate self-poisoning: a retrospective poisons centre study

Introduction Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose–toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre. Methods Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity. Results Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210–10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose–toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity. Discussion All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products. Conclusions Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.

Preparation and sustained-release study of Litsea cubeba essential oil inclusion complex with γ-cyclodextrin-metal–organic frameworks

BackgroundLitsea cubeba essential oil (LCEO) is a food additive that requires encapsulation to delay its release due to its irritating nature. To identify an appropriate inclusion material, gamma (γ)-cyclodextrin (CD)-metal organic frameworks (MOF) were prepared, and the sustained release of the inclusion complex (IC) was studied.ResultsThe γ-CD-MOF was formed using γ-CD, potassium hydroxide (KOH), cetyltrimethylammonium bromide (CTAB), and silane coupling agents through the vapor diffusion method. The highest encapsulated rate achieved was 26.02%, with a temperature of 50 °C, a stirring time of 2.5 h, and an LCEO to γ-CD dosage ratio of 1:8. During the adsorption test, the amount of LCEO gradually increased within the first 180 min. However, after this time, there was no significant change in the adsorption amount of LCEO, indicating that the γ-CD-MOF had reached adsorption equilibrium. The average release rate of the IC reached 9.76% at 11 h. By comparison, the average release rate of the IC with γ-CD was 9.30% at 10 min, resulting in a diffusion index of 0.349. Under ultraviolet (UV) scanning, the sustained-release solution of the IC exhibited a strong characteristic citral absorption peak at 238 nm. Moreover, under infrared spectroscopy scanning, the absorption peak intensity of the IC was 1.19 times higher than that of blank γ-CD-MOF at 1676 cm−1. The IC, as observed through a scanning electron microscope, exhibited round pellets with a diameter of 40–60 μm. Energy dispersive spectroscopy images showed uniform distribution of potassium and sulfur elements. In X-Ray diffraction, the diffraction peaks of the IC were found at 5.27°, 7.45°, 10.54°, 12.08°, 14.20°, 14.92°, 15.84°, 16.68°, 19.24°, 21.80°, and 23.69°, with no significant change in the adsorption amount of LCEO. The Brunauer–Emmett–Teller (BET) testing revealed that the surface area of γ-CD-MOF was 5.089 m2/g, and the pore diameter was 3.409 nm by the Barrett–Joyner–Halenda (BJH) method.ConclusionThese data demonstrated that the sustained effect of the γ-CD-MOF was superior to that of γ-CD. The adsorption kinetics curve followed the Quasi-primary kinetics model, while the release curve adhered to the Ritger–Peppas model. Furthermore, the release behavior was primarily governed by the Fick diffusion mechanism, which was advantageous for achieving the sustained release of LCEO. The UV spectrum, infrared spectroscopy (IR), scanning electron microscopy–energy dispersive spectroscopy (SEM–EDS), X-ray diffraction (XRD), and BET techniques confirmed the successful formation of the IC of LCEO with γ-CD-MOF. This study offers a promising technical solution for delaying the release and improving the sustained-release product of LCEO.Graphical

In Silico Modeling Approaches Coupled with In Vitro Characterization in Predicting In Vivo Performance of Drug Delivery System Formulations.

Optimization of the in vivo performance of dosage forms in humans is essential in developing not only conventional formulations but also drug delivery system (DDS) formulations. Although animal experiments are still useful for these formulations, in silico approaches have become increasingly important for DDS formulations with regard to species-specific differences in physiology that can affect the in vivo performance of dosage forms between animals and humans. Furthermore, it is also important to couple in vitro characterizations with in silico models to predict in vivo performance in humans precisely. In this review article, I summarized in vitro-in silico approaches to predicting the in vivo performance of oral DDS formulations (amorphous solid dispersions, lipid-based formulations, nanosized formulations, cyclodextrins-based formulations, sustained release products, enteric coat products, and orally disintegrating tablets) and parenteral DDS formulations (cyclodextrins-based formulations, liposomes, and inhaled formulations).

GastroPlus- and HSPiP-Oriented Predictive Parameters as the Basis of Valproic Acid-Loaded Mucoadhesive Cationic Nanoemulsion Gel for Improved Nose-to-Brain Delivery to Control Convulsion in Humans.

Oral and parenteral delivery routes of valproic acid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in the brain. A GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in humans. HSPiP software 5.4.08 predicted excipients with maximum possible miscibility of the drug. Based on the GastroPlus and HSPiP program, various excipients were screened for experimental solubility, nanoemulsions, and respective gel studies intended for nasal-to-brain delivery. These were characterized by size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Results showed that in vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively, from both tablets (IR and SR) at 8 h using GastroPlus. The predicted drug access to the portal vein was substantially higher in IR (115 mg) compared to SR (82.6 mg). The plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime sites of the drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested a suitable selection of excipients. The program recommended nasal-to-brain delivery of the drug using a cationic mucoadhesive nanoemulsion. The optimized CVE6 was associated with the optimal size (113 nm), low PDI (polydispersity index) (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7% w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. A penetration study using confocal laser scanning microscopy (CLSM) executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6. This might be attributed to the electrostatic interaction existing between the mucosal membrane and nanoglobules. Thus, cationic nanoemulsions and respective mucoadhesive gels are promising strategies for the delivery of VA to the brain through intransal administration for the treatment of seizures and convulsions.

FORMULATION DEVELOPMENT AND EVALUATION OF ONCE DAILY SUSTAINED RELEASE METFORMIN HYDROCHLORIDE TABLETS

Metformin hydrochloride has relatively short plasma half-life and low absolute bioavailability. The need of administration for two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 20 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic alone or its combination with hydrophobic as rate controlling factor. The tablets were prepared by granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method. The drug release study revealed that HPMC alone was unable to sustain the drug release. Combining HPMC 8 HEC and coting with a semi-permeable membrane with controlled release from an orifice, sustained the drug release for more than 20h.

Microsponges for controlled release and enhanced oral bioavailability of carbamazepine

The oral absorption and hence the oral bioavailability of carbamazepine (CBZ) is variable even after administration of rapidly dissolving formulation. This problem was attributed to supersaturation of CBZ and transformation to the less soluble carbamazepine dihydrate (CBD). Accordingly, formulation of sustained release products of CBZ is a promising approach to overcome this problem. Microsponges are an emerging formulation which can help in this direction. The aim of this work was to optimize the composition of microsponges for better encapsulation and sustained release of CBZ for oral administration. CBZ microsponges were prepared using quasi emulsion solvent diffusion technique with varying composition of ethyl cellulose and polyvinyl alcohol (PVA). Microsponges were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction. Production yield, entrapment efficiency and surface morphology of microsponges were assessed in addition to drug release. Optimum formulation was administered orally to albino rabbits to evaluate the oral bioavailability with reference to unprocessed CBZ. The Instrumental analysis reflected the encapsulation of CBZ in amorphous or molecularly dispersed form in the microsponges. The size and entrapment efficiency of the microsponges increased with increasing polymer contents. This was associated with reduction in CBZ release. Optimum formulation enhanced the oral absorption of CBZ. This was manifested by 2.6-fold increase in the area under the plasma concentration versus time curve compared to that of unprocessed CBZ. The study introduced microsponges as promising carriers for sustained oral delivery of CBZ.

Formulation and Evaluation of Bi-Layer Tablets of Ketorolac Tromethamine

The objective of the present study was to develop and evaluate bi-layer tablets of Ketorolac tromethamine, a nonsteroidal antiinflammatory drug with short half-life, that are characterized by initial burst drug release in the stomach and comply with the release requirements of sustained-release products. Each of the proposed bi-layer tablets is composed of an immediate-release layer and a sustained-release layer, anticipating rapid drug release that starts in the stomach to rapidly alleviate the symptoms and continues in the intestine to maintain protracted analgesic effect. Gastro retentive Bi-Layer tablets of Ketorolac Tromethamine were prepared by using hydrophilic polymers with direct compression on floating – matrix technology and evaluated. Ketorolac tromethamine is freely soluble in water, so it is suitable to develop it as gastro retentive bi-layer tablets using hydrophilic polymers. The developed formulation is equivalent to calculated theoretical drug profile in view of its in vitro release. Immediate release layer was prepared by using dry granulation method in which ac-di sol used as a disintigrant for immediate release of drug. Sustained release layer formulated by using HPMC as release retardant, two grades of HPMC that are HPMC K4M and HPMC K100M used to get sustained release profile for 24 hr. Various trial batches are taken to get desired release profile. Ketorolac tromethamine release from the developed floating formulation followed Higuchi model and nonFickian diffusion is found to be the main mechanism of drug release. The manufacturing procedure was found to be reproducible and formulations were stable after one month of stability studies.
 Keywords: FTIR; Gastro retentive bilayer; ketorolac tromethamine; in vitro release; stability; higuchi.

Nanosuspension Technology for Delivery of Poorly Soluble Drugs and Its Applications: A Review

Now a days, many drug candidates are water insoluble hence they show a limited drug release and poor bioavailability. It is difficult to formulate these drugs by conventional dosage form. Nanosuspension technology is a promising approach to solve the problems of poorly soluble and less bioavailable drugs. Nanosuspension is a very finely colloidal, biphasic, and uniformly dispersed solid drug particles in a suitable aqueous vehicle, having a particle size below 1 μm stabilized by suitable surface active agents and polymers. Nanosuspensions are prepared by various suitable techniques for drug delivery applications. Due to reduced particle size at the nano scale, surface area, saturation solubility, dissolution velocity and bioavailability of BCS class II and class IV drugs are increased sufficiently. Nanosuspension is suitable to administration via various routes such as oral, intravenous, topical, pulmonary and ocular delivery systems. Nanosuspension can be also used for targeting purpose in various diseases such as cancer, HIV and production of sustained and extended release products by choosing suitable polymers. Production and manufacturing are not complicated, easy to scale up. Top down and bottom technologies are used for the preparation of nanosuspensions. It includes methods such as high-pressure homogenization, by milling media method, precipitation method, probe sonication, dry-co-grinding, supercritical fluid method, and lipid emulsion method. Formulation consists of stabilizers, surfactant, and solvents. Nanosuspension can be stored in the form of dry powder using spray drying, freeze drying techniques. This review describes the advantages, various methods of preparation, formulation consideration and characterization of nanosuspension.

In vitro and in vivo assessment of Adansonia digitata mucilage as a matrix former in modified release tablets of metoprolol tartrate

The study was aimed to investigate the ability of Adansonia digitata mucilage (ADM) a new hydrophilic plant polymeric material, in modifying metoprolol tartrate (MPT) release from matrix tablet formulations in comparison with a semi -synthetic polymer-HPMC60SH 4000. Modified release tablets of MPT were directly compressed in the ratios of 1:1 and 1:4 drug/polymer amounts. The tablets properties were evaluated and further, in vivo studies were carried out on 1:4 drug/polymer matrix tablets formulated with ADM and compared with Slow- Lopressor Divitab®. In vitro drug release of MPT was controlled over 24 h for tablets with 1:4 drug/polymer ratios. Release profiles of formulations showed pH independent release and no burst effect at high drug loading. Matrix integrity was maintained throughout dissolution with ADM matrices, an indication of good gel strength contrary to HPMC matrices. Statistical analysis confirmed that MPT release from ADM and HPMC (1:4 drug/polymer) was not significantly different (P > 0.05) likewise similarity factor (f2). The in vivo bioavailability after oral administration of the test formulation (1:4 MPT/ADM) to dogs did not differ significantly from the reference marketed sustained release product.

Sustained Release Drug Delivery System with the Role of Natural Polymers: A review

An appropriately designed sustained release dosage form is opted to be a major goal in solving the problems which arises regarding the targeting of a drug to a specific organ or tissue and for controlling its rate of delivery to the target site. The development of oral sustained release system has proven to be a major challenge to formulation scientist due to their inability to restrain as well as localize the system at targeted areas of the gastrointestinal tract. Therefore the development of matrix type drug delivery system is promising option regarding the development of an oral sustained release system. There is availability of wide variety of polymers which helps the formulation scientist to develop sustained/controlled release products. The attractiveness of these dosage forms is increasing because of their awareness towards toxicity and ineffectiveness when administered by oral route in the form of tablets and capsules. Numerous advantages are provided by sustained release products over conventional dosage forms through optimizing various bio-pharmaceutics, pharmacokinetic and pharmacodynamics properties of drugs and finally leads to reduction in dosing frequency to such an extent that only once daily dose is required for therapeutic management with maximum utility of drug with reduction in both local as well as systemic side effects. They can cure or control diseased condition in shortest possible time with smallest quantity of drug to assure greater patient compliance. Polymer swelling, drug dissolution and its diffusion are the known mechanisms for drug release through polymer network. Keywords: Oral drug delivery system, sustained release dosage form, matrix system, polymer swelling, drug diffusion.

Dissolution Chamber for Small Drug Delivery System in the Periodontal Pocket.

Existing dissolution chambers have relatively large volume compared to the size of the periodontal pocket. A small volume dissolution method that simulates the physiological release environment for periodontal drug delivery is needed. The objectives were to construct a small, more physiologically relevant, dissolution chamber and investigate the properties of the new dissolution chamber for the assessment of sustained drug release systems in periodontal delivery. Flow-through dissolution chambers were constructed using three-dimensional (3D) printing. Drug release experiments were performed using the dissolution chamber and a commercially available long-acting periodontal insert product, PerioChip®. Similar experiments were performed under more traditional larger volume bulk solution conditions for comparison. Computer simulations and experimental results showed that drug clearance from the dissolution chamber was fast compared to drug release from the periodontal product. Drug clearance from the flow-through dissolution chamber and drug release from the sustained release product in the chamber were related to the dissolution medium flow rate and chamber volume. Drug release in the flow-through chamber was slower than that observed in bulk solution, but approached it when the medium flow rate increased. The presence of trypsin in the dissolution medium enhanced drug release from the product. A flow-through dissolution system was constructed that could evaluate drug release from a sustained release product in a small dimension environment by modifying the flow rate and composition of the dissolution medium.

DESIGN AND CHARACTERIZATION OF SUSTAINED RELEASE MATRIX TABLETS OF METFORMIN HYDROCHLORIDE USING COMBINATION OF HYDROPHILIC POLYMERS

Sustained release system is types of modified drug delivery system that can be used as an alternative to conventional system. Among different dosage forms, matrix tablets are widely accepted for oral sustained release Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. They are capable of reducing the dose intake, minimize the blood level oscillation dose related adverse effect and cost thus improves the patient compliance in the therapeutic management of diabetes. The Metformin hydrochloride matrix Sustained release tablets were prepared using different hydrophilic polymers in various proportions as release retarding agent to prolong the drug release and to improve the patience compliance. The tablets were evaluated for various tests like hardness, friability, disintegration and in-vitro dissolution studies. Keywords : Matrix Tablets, Metformin hydrochloride, Hardness, Friability, Disintegration and in-vitro dissolution studies

Twin-screw extrusion of sustained-release oral dosage forms and medical implants.

Most of published reviews of twin-screw extrusion focused on its application for enhancing the bioavailability of amorphous solid dispersions while few of them focused on its use for manufacturing sustained-release oral dosage forms and medical implants, despite the considerable interest and success this process has garnered both in academia and in the pharmaceutical industry. Compared to conventional batch processing, twin-screw extrusion offers the advantages of continuous processing and the ability to prepare oral dosage forms and medical implants that have unique physicochemical and drug release attributes. This review provides an in-depth analysis of the formulation composition and processing conditions of twin-screw extrusion and how these factors affect the drug release properties of sustained-release dosage forms. This review also illustrates the unique advantages of this process by presenting case studies of a wide variety of commercial sustained-release products manufactured using twin-screw extrusion.

Enhancement of dissolution behavior of antiarthritic drug leflunomide using solid dispersion methods

Novel pharmaceutical formulations of antiarthritic drug leflunomide (LEF) with polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) and hydroxypropylmethylcellulose (HPMC) were developed with the aim to improve the LEF dissolution behavior. Solid dispersions were prepared by grinding, freeze-drying and kneading methods and characterized using DSC, XRPD and FTIR spectroscopy. All the investigated polymers were effective in improving the LEF dissolution behavior. Significant increase of the dissolution rate of LEF in its solid dispersions with PVP and PEG was explained by the reduced crystallinity of the drug and solubilizing action of these polymers. An essentially lower dissolution rate of LEF/HPMC solid dispersions was attributed to higher viscosity of dissolution medium due to the presence of HPMC. The results showed that LEF/PVP solid dispersions can be considered as immediate release dosage forms, while LEF/HPMC solid dispersions ban be proposed as a sustained release product for the case when the moderation of drug release is required.

FORMULATION AND BIO-AVAILABILITY PARAMETERS OF PHARMACEUTICAL SUSPENSION

The suspension is a biphasic liquid or semi-solid dosage form where the finely divided insoluble solid drug particles are homogeneously dispersed in a liquid or semi-solid medium. The solid drug particles act here as the dispersed phase and the liquid or the semi-solid as the dispersion medium. Suspensions contribute to pharmaceutical dosage form development by supplying drugs that are insoluble in all acceptable medium and often distasteful. Suspension translates such drugs into more bio-available form when compared to capsules, tablets, coated tablets, enteric coated tablets and sustained release products. The dosage form is palatable to the patient and many are doing well when applied to the skin or mucous membrane. This particular dosage form is also applied for injecting drugs into the systemic circulation. Therefore, pharmaceutical suspension finds its application through three different routes of administration namely oral, externally applied suspension and injectable one. The success of any dosage form largely depends on formulation parameters and the factors that influence the bioavailability which ultimately dictate the therapeutic success of the formulated dosage form. Hence, it is obvious to discuss the formulation parameters and the factors influencing bioavailability of suspension for the therapeutic success of it.

Preparation and in vitro evaluation of a novel chitosan-based hydrogel for injectable delivery of enrofloxacin

BACKGROUND: The development of injectable sustained-release products are of great interest to veterinary pharmaceuticals and animal health business. Recently, great attention has been paid to in situ gel-forming chitosan/beta-glycerophosphate (chitosan/β-GP) solutions due to their good biodegradability and thermosensitivity. OBJECTIVES: The general aim of this study was to prepare a novel in situ gel-forming drug delivery system with a sustained release profile for enrofloxacin. METHODS: Chitosan, β-GP and enrofloxacin were used in different concentrations and six formulations of chitosan/β-GP were prepared. The properties of the hydrogels including the pattern of drug release, gelation time, syringeability, morphology, FTIR spectra, and in vitro antimicrobial activity were evaluated. RESULTS: The release rate of enrofloxacin from the hydrogels and syringeability of the final solutions were decreased by increasing in β-GP and chitosan concentrations. All formulations could release the drug up to 120 hours but formulation 1 (chitosan-2%, β-GP-5% and enrofloxacin-1%) gave the best results based on its optimal drug release profile and viscosity. The FTIR studies showed that there were no interactions between enrofloxacin and hydrogel excipients. Scanning electron microscopy showed that the formed gel had a continuous texture, while the swelled gel in phosphate buffer had a porous structure. Microbiological tests revealed high bactericidal activities for this enrofloxacin- loaded hydrogel which were comparable to those of positive control (enrofloxacin suspension) in terms of inhibition zone, MIC and MBC values. CONCLUSION: Because of simple preparation and sustained release profile of the drug, this hydrogel could be a promising delivery system for enrofloxacin in animals.

A Novel Manufacturing Method for Sustained Release Products and Modelling Dissolution

A novel processing method for the manufacturing of slow-release particles is proposed. The method is based on the wet milling of active compounds and the selected biodegradable polymers combined with subsequent drying. In the proposed method the dissolution barrier is processed in one step compared to traditional methods consisting of several steps. The experimental dissolution curves of natural polymer (native potato starch and lignin) coated salts were compared with unmilled and milled salts. The dissolution process model was developed in order to characterize and to design sustained release particles. Models were verified with the existing dissolution data. Verified models combined with SEM-images could support the proposed dissolution mechanisms for different polymers. Estimates of effective surface area and diffusion layer thickness (active surface model) and effective diffusivity and gelling layer thickness (constant gel radius model) is achieved.

Policy implications for multipurpose prevention technologies service delivery.

Policy implications for multipurpose prevention technologies service delivery.

Sustained-release from nanocarriers: a review.

Nanocarriers have been explored for delivering drugs and other bioactive molecules for well over 35years. Since the introduction of Doxil®, a nanoliposomal delivery system for the cancer drug doxorubicin, several products have been approved worldwide. The majority of these products focus on cancer chemotherapy, and utilize the size advantage of nanocarriers to obtain a favourable distribution of the drug carrier in the human body. In general, such carriers do not sustain drug release over more than a few days at best. In this review, we explore the reasons for this, and present an overview of successful research that is capable of generating sustained-release products in non-cancer applications. A variety of nanocarriers have been studied, and their advantages and shortcomings are highlighted in this review. The achievement of sustained release of bioactive molecules opens new doors in nanotherapeutics.

Preparation and evaluation of sustained-release azithromycin tablets in vitro and in vivo

The objective of this study was to prepare azithromycin (AZI) sustained-release products in order to allow for a high dose to be administered, reduce gastrointestinal side-effects and increase the compliance of patients. AZI sustained-release tablets with different release performance (F-I: T100% = 3 h and F-II: T100% = 8 h in pH 6.0 phosphate buffer) were successfully prepared by wet granulation. The in vitro release rate and drug release mechanism were studied. The release rate of F-I was affected by dissolution media with different pH, but not for F-II. Hixson–Crowell model was the best regression fitting model for F-I and F-II. Additionally, F-I and F-II both belonged to non-Fick diffusion. Oral pharmacokinetics of the two tablets and one AZI dispersible tablet as reference were studied in six healthy beagle dogs after oral administration. Compared with the reference, the Cmax of F-I and F-II were decreased, and the Tmax were prolonged, in that case which meet the requirement of sustained-release tablets. The relative bioavailability of F-I and F-II were 79.12% and 64.09%. T-test of AUC0–144, and AUC0–∞ for F-I and F-II indicated there was no significant difference between F-I and F-II. These mean that the extended release rate did not induce different pharmacokinetics in vivo.