ABSTRACT
This study was designed to formulate, for the first time, metformin hydrochloride (MH, 850 mg/tablet) as a controlledporosity osmotic pump (CPOP) system to achieve zero-order release pattern. MH core tablet was coated with celluloseacetate membrane containing PEG 400. The effect of different percentages and molecular weights of polyethyleneoxide (PEO, 900K and 4M) in tablet core was studied. The United States Pharmacopeia (USP) apparatus II andphosphate buffer pH 6.8 were used for the release studies; meanwhile, a promising formula was tested in biorelevantmedia. The stability of some selected formulations was carried out for 6 months, at bench and accelerated conditions.Evaluation included: MH content, Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM),drug release, and kinetics. Results revealed that increasing PEO percentage within the core decreased MH release.SEM verified formation of pores in the membrane that accounts for MH release. Almost all stored tablets werestable for all studied parameters. MH endothermic peak maintained its position and energy of enthalpy on storageas confirmed by DSC. MH release rate from a promising formula, following zero-order release model, increased by28% in biorelevant media compared to phosphate buffer. Subsequently, in vitro release in biorelevant media could beemployed as a tool to anticipate in vivo tone of CPOP formulations
ABSTRACT
An HPLC/UV method to monitor meloxicam (MX) in human plasma was developed and properly validated. This method was based on a reversed-phase chromatographic analysis using C18-Symmetry column and a mobile phase consisting of acetonitrile: deionized water [50:50 (% v/v)] adjusted to pH 3 with glacial acetic acid. The detection wavelength was 360 nm using piroxicam as an I.S. The developed HPLC method was linear, sensitive, accurate, precise, selective and stable. This method exclusively provided a LLOQ of 5 ng/mL and ULOQ of 3000 ng/ml which could be considered as an excellent and economical method for carrying-out BA/BE studies. The determination of pharmacokinetics of single oral dose (15 mg/tablet) administered to healthy human male volunteer was carried-out to compare the bioavailability of three different MX products with a washout period of 8-days between treatments. Moreover, a comparative in vitro dissolution study of the three products using USP#4 (the Flow-through cell, FTC) has been carried-out prior to the in vivo test. The pharmacokinetic data revealed that the developed HPLC method was sensitive enough to monitor the multiple-peak phenomena characterized for MX absorption. Where, the first Cmax appeared at 4.5–5.5 hrs and the second at 10–12 hrs, for the tested products. Abbreviations: MX: Meloxicam, I.S.: Internal Standard, Q: Amount Dissolved, IR: Immediate Release, LOQ: Lower limit of quantification, ULOQ: Upper limit of quantification, BA: Bioavailability, BE: Bioequivalence.
ABSTRACT
This study explored the effect of nano-crystalline cellulose (NCC) on Meloxicam (MX) solid dispersion (SD) prepared by co-grinding technique compared to micro-crystalline cellulose (MCC) in presence of lactose. MX-tablets were prepared by direct compression of different co-ground SDs or physical mixtures. The solubility, dissolution, SEM and DSC of different preparations were studied. Flow-through cell apparatus (FTC) was used to study the dissolution of MX from tablets at pH 7.4. Generally, the results revealed that increasing NCC loadings showed a direct increase in both the solubility and dissolution of MX. MCC did not improve either the solubility or the dissolution of MX in the physical mixture, while, co-grinding dramatically decreased the dissolution rate of MX. It was interesting to find that grinding of MX-powder alone or in a mixture with lactose highly increased MX solubility and dissolution. SEM as well as DSC were found to be very good tools, without a single exception, to describe the observed solubility and dissolution of MX in these proposed preparations. SEM-images showed the particle size reduction upon grinding or co-grinding techniques. While DSC-data proved that the crystalline structure of MX has been changed to an amorphous state.
ABSTRACT
The aim of this study is to investigative the stability of poly(ethylene oxide) (PEO) matrix tablets containing diltiazem hydrochloride (DTZ) after five-year storage at room temperature. DTZ matrix tablets containing different molecular weights (MW) of PEO and electrolytes (sodium carbonate anhydrous Na2CO3, potassium chloride KCl and pentasodium tripolyphosphate anhydrous PSTPP) were prepared. The fresh and stored tablets were evaluated by DTZ content, in vitro drug release rates and kinetics as well as DSC. All the PEO’s matrix tablets showed no significant changes in release rate, kinetics and drug content. The release rates of DTZ following five-year storage were slightly increased as the MW of PEO increased from 900,000 to 8,000,000. Also, it was clear that the addition of electrolyte drastically slowed the release rates of DTZ from fresh and stored tablets. DSC thermograms and similarity factor (ƒ2) depicted good system stability for all stored tablets. This is the first five-year long-term stability study reported concerning DTZ/PEO matrix tablets with different MW, which proved its stability for several years. This study might throw light on the dramatic difference observed between this study and the reported data of accelerated stability testing under stress conditions found in the literature.