In vitro and in vivo evaluations of a novel pulsed and controlled osmotic pump capsule

Objective: For better treatment of circadian cardiovascular events, a novel Propranolol hydrochloride (PNH) delayed-release osmotic pump capsule was developed.

Methods: The capsule body was designed of asymmetric membrane and the capsule cap was made impermeable. The physical characteristics of capsule body walls and membrane permeability were compared among different coating solutions.

Results: The formulation with the glycerin and diethyl phthalate (DEP) ratio of 5:4 appeared to be the best. The lag time and subsequent drug release were investigated through assembling the capsule body with capsule caps of different length. WSR N-10 was chosen as the suspending for its moderate expanding capacity. The influence of factors (WSR N-10 content, NaCl content and capsule cap length) on the responses (lag time and drug release rate) was evaluated using central composite design-response surface methodology. A second-order polynomial equation was fitted to the data and actual response values were in good accordance with the predicted ones. The optimized formulation displayed complete drug delivery, zero-order release rate with 4-h lag time. The results of in vivo pharmacokinetics in beagle dogs clearly suggested the controlled and sustained release of PNH from the system and that the relative bioavailability of this preparation was about 1.023 comparing the marketed preparation.

Conclusions: These results indicate that by the adjustment of capsule cap length, PNH could be developed as a novel pulsatile and controlled drug delivery system.     

Anti-hyperuricemic property of 6-shogaol via self-micro emulsifying drug delivery system in model rats: formulation design,in vitro and in vivo evaluation

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00?±?0.26?nm and 0.18?±?0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.     

Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect

The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10, and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation. The prepared formulations were further characterized by the droplet size, self-microemulsifying time, zeta potential, polydispersity index (PDI), and robustness to dilution. The in vitro release profile of cinacalcet-SMEDDS was determined in four different release medium and in fasted state and fed state of simulated gastrointestinal fluid. Cinaclcet-SMEDDS were implemented under fed and fasted state in dogs and product REGPARA^® was used as a comparison to the prepared formulation in the pharmacokinetics. The result showed the components of SMEDDS, the amount of oil, the ratio of surfactant, and co-surfactant was optimized using solubility, pseudo-ternary phase diagram studies, and response surface methodology. In vitro drug release studies indicated that the cinacalcet-SMEDDS eliminated the effect of pH variability in release medium and variational gastroenteric environments with improved drug release performance. Pharmacokinetic studies revealed that the profiles of cinacalcet-SMEDDS were similar both in the fasted and fed state compared with commercial product, indicating the formulation significantly promoted the absorption, enhanced bioavailability and had no food effect essentially. It is concluded that poorly water-soluble drug cinacalcet was improved in the solubility and bioavailability by using a successful oral dosage form the SMEDDS, and eliminated food effect as well.     

Solid carriers for improved solubility of glipizide in osmotically controlled oral drug delivery system

The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli-PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli-PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli-PVP solid dispersion system has suitable solubility behavior in EOP tablets.     

Synchronized and controlled release of metformin hydrochloride/glipizide from elementary osmotic delivery

Abstract

The combination of metformin hydrochloride (MTF) and glipizide (GLZ) is second-line medication for diabetes mellitus type 2 (DMT2). In the present study, elementary osmotic pump ( EOP) tablet is designed to deliver the combination of MTF and GLZ in a sustained and synchronized manner. By analyzing different variables of the formulation, sodium hydrogen carbonate is introduced as pH modifier to improve the release of GLZ, while ethyl cellulose acts as release retardant to reduce the burst release phase of MTF. A two-factor, three-level face-centered central composite design (FCCD) is applied to investigate the impact of different factors on drug release profile. Compared with conventional tablets, the EOP tablet demonstrates a controlled release behavior with relative bioavailability of 99.2% for MTF and 99.3% for GLZ. Data also shows EOP tablet is able to release MTF and GLZ in a synchronized and sustained manner both in vitro and in vivo.     

Design of a timed and controlled release osmotic pump system of atenolol

The objective of the article was to design a novel timed and controlled release osmotic pump (TCOP) containing atenolol as an active pharmaceutical ingredient and compare with a bilayer-core osmotic pump (BCOP) of atenolol. Different from BCOP, a modulating barrier was added to delay the drug release and obtain desired lag time (T_lag). The influences of the amount of pore-forming agent and modulating barrier, coating weight gain on the lag time (T_lag) and drug release rate (R_t) of TCOP were investigated. The central composite design-response surface methodology (RSM) was applied to optimize the formulation. Rhodamine B was added to modulating barrier to determine the release process of modulating barrier. A method used to correct the release profiles with a certain lag time by ΔT_lag and interpolating was applied to compare TCOP with BCOP. T_lag was directly proportional to the amount of modulating barrier and coating weight gain, but inversely related to the amount of pore forming agent, which were contrary to the effects on R_t. The optimal formulation including 60?mg PEO WSR N80, 3?g PEG 4000 and 6% coating weight gain could obtain a 3.59-h T_lag. According to the release of Rhodamine B, the modulating barrier was completely pushed out at ～5.0?h, longer than 3.59?h, therefore, atenolol along with remaining modulating barrier was released together between 3.59 and 5.0?h. By comparing with BCOP, the release profiles subtracting the part of lag time had no significant difference, yet R_t of TCOP presented a slight decrease.     

Evaluation of monolithic osmotic tablet system for nifedipine delivery in vitro and in vivo

The aim of this study was to evaluate the monolithic osmotic tablet system (MOTS) containing a solid dispersion with the practically water-insoluble drug nifedipine in vitro and in vivo. In the drug release study in vitro, the release profiles of this system had almost zero-order kinetics. The influences of tablet formulation variables, sizes of the delivery orifice, membrane variables, and values of pH in the dissolution medium on nifedipine release from MOTS have been investigated. The results provided evidence that the tablet core played an important role in MOTS. While orifice sizes and membrane variables affected the nifedipine release rate, MOTS was independent of the dissolution medium. The appropriate orifice size was found to be in the range of 0.5-1.0 mm. The coating membrane incorporating hydrophilic polyethylene glycol (PEG) formed a porous structure. The human pharmacokinetics and relative bioavailability of MOTS containing nifedipine were compared with a commercial Adalat® osmotic tablet system containing an equivalent dose of nifedipine following an oral single dose of 30 mg given to each of 11 healthy volunteers in an open, randomized crossover study in vivo. The relative bioavailability for MOTS was 112%. There was no statistically significant difference in the pharmacokinetic parameters between two dosage forms. It is concluded that the monolithic osmotic tablet controlled release system is feasible for a long-acting preparation as a once-daily treatment.     

Novel taste-masked orally disintegrating tablets for a highly soluble drug with an extremely bitter taste: design rationale and evaluation

The purpose of this study was to evaluate the taste masking potential of novel solid dispersions (SDs) using Eudragit^® EPO as the excipient when incorporated into the orally disintegrating tablets (ODTs) for delivering a highly soluble drug with an extremely bitter taste. The pyridostigmine bromides (PB) SDs (PBSDs) were prepared by solvent evaporation–deposition method. The physicochemical properties of PBSDs were investigated by means of differential scanning calorimetry and Fourier transformed infrared spectroscopy. The dissolution test showed that only about 8% of PB was released from PBSDs in the simulated salivary fluid in 30 s. Therefore, PBSDs were considered taste-masked and selected for formulation of PBODTs. A central composite design was employed for process optimization. Multiple linear regression analysis for process optimization revealed that the optimal PBODTs were obtained, when the microcrystalline cellulose and crospovidone were 17.16 and 5.55 (%, w/w), respectively, and the average in vivo disintegration time was 25 s. The bitterness threshold of PB was examined by a sensory test, and the threshold value was set as 3?mg in each tablet. Taste evaluation of PBODTs in 18 volunteers revealed considerable taste masking with bitterness below the threshold value. PBODTs also revealed rapid drug release (around 99%, 2?min) in the simulated gastric fluid. The mean PB plasma concentration–time profiles of PBODTs and that of the commercial tablets were comparable, with closely similar pattern. Bioequivalence assessment results demonstrated that PBODTs and the commercial tablets were bioequivalent. In conclusion, PBODTs are prepared successfully, with taste masking and rapid disintegration in the oral cavity.     

Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug delivery and reduced variability in oral bioavailability

The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too.     

Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation

The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f₂). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14?h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation.     

Application of scCO2 technology for preparing CoQ10 solid dispersion and SFC-MS/MS for analyzing in vivo bioavailability

Objective: In this study, solid dispersion (SD) for oral delivery of a poorly water-soluble drug, coenzyme Q10 was developed by supercritical fluid technology and characterized in vitro and in vivo.

Methods: Dissolution was used to optimize the formulations of CoQ10-SD. The physicochemical properties of SD were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The supercritical fluid chromatography–electrospray ionization tandem mass spectrometry (SFC–ESI-MS/MS) was used for the in vivo study.

Results: The results of DSC and PXRD indicated that the drug in SD was in amorphous state. In vitro drug release, the dissolution of coenzyme Q10 in solid dispersion improved to 78.8% compared with commercial tablets of 0.16%. The area under c–t curve (AUC_0–72h) and mean maximum concentrations (C_max) of CoQ10-SD were 2.43-fold and 3.0-fold, respectively higher than that of commercial tablets in rats, confirming improved bioavailability.

Conclusion: Supercritical fluid technology was successfully used for the preparation and analysis of CoQ10-SD for the first time and significantly improved the dissolution and bioavailability of coenzyme Q10.     

PVP and surfactant combined carrier as an effective absorption enhancer of poorly soluble astilbin in vitro and in vivo

Context: Astilbin is considered to be a new and promising immunosuppressant for immune related diseases, but limited in clinical application due to its poor water solubility, difficult oral absorption and low bioavailability.

Objective: The present work studied the effect of PVP and surfactant combined carrier on its capability to improve drug absorption.

Materials and methods: PVP K30-Tween 80 combined carries was applied into the astilbin solid dispersions, tested both in vivo in beagle dogs and in vitro in transport experiments across Caco-2 cell monolayers.

Results and discussion: In the animal studies a many fold increase in plasma AUC was observed for the solid dispersions of drug in PVP K30-Tween 80 combined carries compared to active pharmaceutical ingredient (API). The applicability of Caco-2 monolayers as a tool for predicting the in vivo transport behavior of Astilbin in combination with a solubility enhancing carries was shown. In vitro transport studies confirmed the effect of combined carries on the absorption behavior of the astilbin. MTT studies showed the cell viability gradually decreased with the increase of the drug concentration in a dose dependent manner for astilbin and that in solid dispersions. The permeability and apparent permeability coefficients (P_app) increased with drug in the Caco-2 cell.

Conclusion: In this study, it was found that PVP K30 and Tween 80 promoted the permeability of drugs best within a certain amount. For astilbin PVP K30 and surfactant combined carrier had a strong potential to improve oral bioavailability.     

绿原酸磷脂复合物固体分散体的体外溶出和药动学研究

为研究绿原酸磷脂复合物固体分散体(CA-PC-SD)的体外溶出以及体内药动学规律,采用HPLC法考察CA-PC-SD的体外溶出,大鼠灌胃后测定其血药浓度,并采用DAS 2.0软件分析计算药动学参数.结果显示:CA-PC-SD显著改善绿原酸磷脂复合物(CA-PC)的溶出效果,相较于原料药(CA)其相对生物利用度提高2.12倍.表明CA-PC-SD能显著改善CA-PC的体外溶出特性以及CA的口服生物利用率.     

Wet process-induced phase-transited drug delivery system: a means for achieving osmotic, controlled, and level A IVIVC for poorly water-soluble drug

A phase-transited, nondisintegrating, controlled release, asymmetric membrane capsular system for poorly water-soluble model drug flurbiprofen was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. Asymmetric membrane capsules (AMCs) were prepared using fabricated glass mold pins through wet phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies for all the prepared formulations were carried out (n = 6). Statistical test was applied for in vitro drug release at p > .05. Predicted in vivo concentration from in vitro release data closely matched the minimum effective concentration (in vivo) level achieved by the drug from its release through phase-transited AMC in rabbits for the first hour. The drug release was found to be independent of the pH but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed level A correlation (R(2) > .99) with 42.84% relative bioavailability compared to immediate release tablet of flurbiprofen. Excellent correlation achieved suggested that the in vivo performance of the AMCs could be accurately predicted from their in vitro release profile.     

Effect of semicrystalline polymers on self-emulsifying solid dispersions of nateglinide: in vitro and in vivo evaluation

This study was undertaken to improve solubility and bioavailability of nateglinide by preparation of stable self-emulsifying solid dispersions (SESDs). The influence of semicrystalline polymers (poloxamer 407, gelucire 50/13) and method of preparation on dissolution behavior, in vivo performance and stability of nateglinide SESDs were investigated. After optimization, SESDs were prepared at 1:5 weight ratio of nateglinide and polymer individually. All the SESDs were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Aqueous solubility of nateglinide was enhanced by 91.82-fold. The SESDs (poloxamer 407-based solid dispersions) achieved rapid and complete drug release (～100% within 45?min) at pH 2. The improved dissolution appeared to be well correlated with the enhanced bioavailability of nateglinide in rabbits. After oral administration of SESDs (poloxamer 407-based solid dispersions), C_max and AUC of nateglinide were increased by ～2.92 and 1.77-folds, respectively, signifying the effectiveness of solid dispersions to improve the bioavailability of nateglinide. Stability during storage was established to show prevention of recrystallization. In conclusion, SESDs with poloxamer 407 in solvent method appeared to be an economic and promising technique to improve the dissolution, bioavailability, and stability of nateglinide.     

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation,characterization, in vitro,and in vivo study

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD₅₀). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.     

A pH-independent instantaneous release of flurbiprofen: a study of the preparation of complexes,their characterization and in vitro/in vivo evaluation

In this study, furbiprofen/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes were prepared to improve the drug dissolution and facilitate its application in hydrophilic gels. Inclusion complexes were prepared using a supercritical fluid processing and a conventional optimized co-lypholization method was employed as a reference. The entrapment efficacy and drug loading of both methods were investigated. Evaluation of drug dissolution enhancement was conducted in deionized water as well as buffer solutions of different pH. Carbopol 940 gels of both flurbiprofen and flurbiprofen/HPβCD inclusion complexes, with or without penetration enhancers, were prepared and percutaneous permeation studies were performed using rat abdominal skin samples. Formation of flurbiprofen/HPβCD inclusion complexes was confirmed by Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The results obtained showed that SCF processing produced a higher EE (81.91?±?1.54%) and DL (6.96?±?0.17%) compared with OCL with values of 69.11?±?2.23% and 4.00?±?1.01%, respectively. A marked instantaneous release of flurbiprofen/HPβCD inclusion complexes prepared by SCF processing (103.04?±?2.66% cumulative release within 5?min, a 10-fold increase in comparison with flurbiprofen alone) was observed. In addition, this improvement in dissolution was shown to be pH-independent (the percentage cumulative release at pH 1.2, 4.5, 6.8 and 7.4 at 5?min was 95.19?±?1.71, 101.75?±?1.44, 105.37?±?4.58 and 96.84?±?0.56, respectively). Percutaneous permeability of flurbiprofen-in-HPβCD-in-gels could be significantly accelerated by turpentine oil and was related to the water content in the system. An in vivo pharmacokinetic study showed a 2-fold increase in C_max and a shortened T_max as well as a comparable relative bioavailability when compared with the commercial flurbiprofen Cataplasms (Zepolas^®). With their superior dissolution, these flurbiprofen/HPβCD inclusion complexes prepared by SCF processing could provide improved applications for flurbiprofen.     

Preparation,characterization and in vitro and in vivo evaluation of a solid dispersion of Naringin

Naringin (NA) is one of typical flavanone glycosides widely distributed in nature and possesses several biological activities including antioxidant, anti-inflammatory, and antiapoptotic. The aim of this study was to develop solid dispersion (SD) and to improve the dissolution rate and oral bioavailability of NA. NA–SD was prepared by the traditional preparation methods using PEG6000, F68, or PVP K30 as carrier at different drug to carrier ratios. According to the results of solubility and in vitro dissolution test, the NA–PEG6000 (1:3) SD was considered as an optimal formulation to characterize by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry and powder X-ray diffraction. Furthermore, oral bioavailabilities of NA–PEG6000 (1:3) SD and NA–suspension with the same dosage were investigated in SD rats. The results confirmed the formation of SD and the pharmacokinetic parameters of NA–PEG6000 (1:3) SD (C_max?=?0.645?±?0.262?µg/ml, AUC_0–t?=?0.471?±?0.084?µg/ml?h) were higher than that of NA–suspension (C_max?=?0.328?±?0.183?µg/ml, AUC_0–t =?0.361?±?0.093?µg/ml?h). Based on the results, the SD is considered as a promising approach to enhance the dissolution rate and oral bioavailability of NA.     

Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation,in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits

A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68?±?1.3). All the prepared formulae had particle size less than 500?nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30?mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1?h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn’t exceed 35% during the first hour reaching a 85% of the drug released at the end of 24?h. A7 was selected for the in vivo study; T_max of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity.