Design and Optimization of Pioglitazone Hydrochloride Self-Nanoemulsifying Drug Delivery System (SNEDDS) Incorporated into an Orally Disintegrating Tablet (original) (raw)
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International journal of pharma and bio sciences, 2017
Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility-with extensive first-pass metabolism-can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT14) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT14) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT14) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.
Asian Journal of Pharmaceutics, 2014
S elf-microemulsifying drug delivery system (SMEDDS) is a promising system for the Biopharmaceutics Classification System (BCS) class II drugs. The current research aimed to improve the dissolution of poorly water-soluble antidiabetic drug pioglitazone HCl by formulating it in SMEDDS. Liquid SMEDDS of pioglitazone HCl were formulated with Capmul MCM C8 and oleic acid as oil phase, Cremophor RH 40 and Tween 80 as surfactant phase, and Transcutol P as cosurfactant phase after screening various vehicles. The prepared formulations were evaluated for self-emulsifying ability and phase diagram was constructed to optimize the system. These systems were further characterized for globule size, effect of pH and robustness, zeta potential, drug content, viscosity, self-emulsification time, polydispersity index, % transmittance, thermodynamic stability, surface morphology, and drug release. The system was robust to different pH media and dilution volumes. The optimized system possessed a mean globule size of 122.2 nm, zeta potential around-22.9 mV, drug content 99.66 ± 0.47%, viscosity 0.8874 ± 0.026 cP, emulsification time 38 s, polydispersity index value of 0.5, and transmittance value of 99.3 ± 0.6%. Drug release in hydrochloric acid buffer pH 2 was found to be 99.35 ± 0.38%. More than threefold increase in dissolution characteristics of pioglitazone HCl in SMEDDS was observed as compared to pure and marketed formulation. Liquid SMEDDS filled in hard gelatin capsule (HGC) shell was found to be compatible. Stability studies show there was no sign of phase separation or precipitation and no change in drug content was observed.
The present investigation was focused on formulation and in vitro evaluation of mouth dissolving tablets (MDTs) of Pioglitazone Hydrochloride (PGTZN) thereby enhancing the dissolution rate. MDTs were prepared by wet granulation and direct compression methods using Croscarmellose sodium, Crospovidone and Sodium starch glycolate as superdisintegrants. Powder blends were evaluated for flowability and all the powder blends showed acceptable flowability. The prepared tablets were evaluated for post compression parameters like hardness, friability, wetting time and showed acceptable results. Formulations F8 and F15 showed disintegration time of 23 and 22 sec respectively. Dissolution was performed in pH 1.2 HCl buffer and formulations F15 showed maximum drug release within 30 min. drug release from F15 was more than that of the marketed drug. Hence, it could be concluded that formulation F15 showed good drug release than marketed drug and there is a lot of scope for future in vivo studies.
2013
Many drugs are abandoned due to poor aqueous solubi lity, although having a potential therapeutic effec t. Numerous methods have been followed to improve the dissoluti on rate of poorly water soluble drugs. Solid disper ion is successfully applied to improve the solubility and consequently the bioavailability of poorly water so luble drugs. The aim of present study was to prepare solid dispe rsions of Pioglitazone HCl with PEG 6000, PVP, Polo xamer 407, Eudragit EPO and HPMC and determine the effect of those polymers on dissolution of pioglitazone H Cl. solid dispersion of Pioglitazone HCl was prepared by solv ent evaporation method. Solid dispersions were eval uated with respect to their yield percentage, percent drug con tent, FT-IR spectra and in vitro dissolution studie s. The histogram response, descriptive statistics of response ensure the fitness of the experiment. The result obtained show that the dissolution profile of Pioglitazone HCl solid dispe rsion was considerably imp...
Formulation and Evaluation of Mouth Dissolving Tablets of Pioglitazone
2013
This study aims to fabricate and optimize mouth dissolving tablets prepared by direct compression to not only have sufficient mechanical strength/hardness to withstand manual handling, but also have a rapid disintegration time. This research was to develop fast dissolving tablets of pioglitazone. Tablets containing pioglitazone, β-Cyclodextrin and Sodium starch glycolate were prepared by direct compression technique. The tablets were evaluated for thickness, weight variation, hardness, percentage friability, wetting time, disintegration time and drug release studies. Formulations having superdisintegrants in different concentrations levels were prepared to access their efficiency. Tablets containing β-Cyclodextrin is showing excellent results as compare to other formulations.
Solubility and Dissolution Enhancement of Pioglitazone Using Solid Dispersion Technique
International Journal of Current Pharmaceutical Research
Objective: To design the study to improve the solubility and hence enhance the dissolution of hydrophobic drug Pioglitazone in order to increase its bioavailability.Methods: Solid dispersion of Pioglitazone using carriers Poloxomer 188 and HPβCD was formulated in different ratios by microwave induced fusion method. In particular, the Microwave technology has been considered in order to prepare an enhanced release dosage form for poorly water soluble drug Pioglitazone. Statistical Analysis: Their physicochemical characteristics and solubility were compared to the corresponding dispersions and marketed drug. Drug and polymer were further characterized by FTIR.Results: The results of FTIR revealed that no chemical interaction between the drug and the polymer exist.Conclusion: All the formulations showed a marked increase in drug release with the increase in the concentration of Poloxomer 188 and HPβCD.Â
Journal of Advanced Pharmaceutical Technology & Research, 2012
Investigation of in vitro/in vivo behavior of fast-dissolving tablets containing solid dispersions of pioglitazone hydrochloride (PIO) is the focus of the present research work. The effect of various hydrophilic polymers on the aqueous solubility of PIO was studied. Poly vinyl pyrrolidine K 30 (PVPK 30) carrier was selected and solid dispersions were prepared by various methods. Evaluation of solid dispersion for percentage yield, drug content, solubility, and Fourier Transform Infrared-indicated kneading method was most appropriate. Furthermore, the dissolution studies exhibited an enhancement in drug dissolution. One-way ANOVA of in vitro data suggested that there was significant (P ≤ 0.05) difference in dissolution profile of PIO solid dispersion when compared with pure drug and commercial product. Infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction performed on solid dispersion indicated lack of physicochemical interaction between the drug and the carrier. The selected formulation is compressed into fast-dissolving tablets which were further evaluated for tablet properties and in vitro drug release. In vivo studies of pure drug, selected formulation, and marketed product were carried out in male Wistar rats and pharmacokinetic parameters were calculated using Kinetica software 2000. The best formulation has shown T max of 1 hour which was highly significant (P < 0.01) when compared with pure drug and marketed formulation. Therefore, the solid dispersions prepared by kneading method using PVPK 30 as hydrophilic carrier can be successfully used for improvement of dissolution of PIO and resulted in faster onset of action as indicated by in vivo studies.
The present study was aimed to formulate the solid dispersion incorporated microcapsule to improve the dissolution rate and half life of pioglitazone hydrochloride. The solvent evaporation method was used to formulate the solid dispersion resulted increased dissolution rate, bioavailability and stability. Finally increase the half life of the drug by employ the orifice ionic gelation method to formulate solid dispersion incorporated muco-adhesive microcapsule. The solubility of pioglitazone hydrochloride was increase by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 using solvent evaporation methods. The microcapsules of pioglitazone hydrochloride were prepared by (orifice ionic gelation method) employing sodium alginate as a cell forming polymer and using a different bio-adhesive polymers as carbopol, HPMC and sodium CMC in a various ratios of 1:1, 3:1, 6:1 & 9:1, by orifice ion gelation method. FT-IR spectra revealed no chemical incompatibility between drug and polymers. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), Powder X-Ray Diffraction (PXRD). Scanning electron microscope photographs of samples revealed that all prepared microcapsules were almost spherical in shape and have a slightly smooth surface.
Nanoemulsifying drug delivery system to improve the bioavailability of piroxicam
Pharmaceutical Development and Technology, 2016
The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy. Materials and methods: The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets. Results and discussion: The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (Feldene®) (CD). The relative bioavailability of S-sSNEDDS (F12) relative to PP or CD was about 151.01% and 98.96%, respectively. Conclusion: The obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.
FAST DISSOLVING TABLETS PIOGLITAZONE
This study aims to fabricate and optimize mouth dissolving tablets prepared by direct compression to not only have sufficient mechanical strength/hardness to withstand manual handling, but also have a rapid disintegration time. This research was to develop fast dissolving tablets of pioglitazone. Tablets containing pioglitazone, β-Cyclodextrin and Sodium starch glycolate were prepared by direct compression technique. The tablets were evaluated for thickness, weight variation, hardness, percentage friability, wetting time, disintegration time and drug release studies. Formulations having superdisintegrants in different concentrations levels were prepared to access their efficiency. Tablets containing β-Cyclodextrin is showing excellent results as compare to other formulations.