Abstract: A new and cost effective RP-HPLC method was
developed and validated for simultaneous analysis of non steroidal
anti inflammatory dugs Diclofenac sodium (DFS), Flurbiprofen
(FLP) and an opioid analgesic Tramadol (TMD) in advanced drug
delivery systems (Liposome and Microcapsules), marketed brands
and human plasma. Isocratic system was employed for the flow of
mobile phase consisting of 10 mM sodium dihydrogen phosphate
buffer and acetonitrile in molar ratio of 67: 33 with adjusted pH of
3.2. The stationary phase was hypersil ODS column (C18, 250×4.6
mm i.d., 5 μm) with controlled temperature of 30 C°. DFS in
liposomes, microcapsules and marketed drug products was
determined in range of 99.76-99.84%. FLP and TMD in
microcapsules and brands formulation were 99.78 - 99.94 % and
99.80 - 99.82 %, respectively. Single step liquid-liquid extraction
procedure using combination of acetonitrile and trichloroacetic acid
(TCA) as protein precipitating agent was employed. The detection
limits (at S/N ratio 3) of quality control solutions and plasma samples
were 10, 20, and 20 ng/ml for DFS, FLP and TMD, respectively.
The Assay was acceptable in linear dynamic range. All other
validation parameters were found in limits of FDA and ICH method
validation guidelines. The proposed method is sensitive, accurate and
precise and could be applicable for routine analysis in
pharmaceutical industry as well as in human plasma samples for
bioequivalence and pharmacokinetics studies.
Abstract: A new reverse phase-high performance liquid chromatography (RP-HPLC) method with fluorescent detector (FLD) was developed and optimized for Norfloxacin determination in human plasma. Mobile phase specifications, extraction method and excitation and emission wavelengths were varied for optimization. HPLC system contained a reverse phase C18 (5 μm, 4.6 mm×150 mm) column with FLD operated at excitation 330 nm and emission 440 nm. The optimized mobile phase consisted of 14% acetonitrile in buffer solution. The aqueous phase was prepared by mixing 2g of citric acid, 2g sodium acetate and 1 ml of triethylamine in 1 L of Milli-Q water was run at a flow rate of 1.2 mL/min. The standard curve was linear for the range tested (0.156–20 μg/mL) and the coefficient of determination was 0.9978. Aceclofenac sodium was used as internal standard. A detection limit of 0.078 μg/mL was achieved. Run time was set at 10 minutes because retention time of norfloxacin was 0.99 min. which shows the rapidness of this method of analysis. The present assay showed good accuracy, precision and sensitivity for Norfloxacin determination in human plasma with a new internal standard and can be applied pharmacokinetic evaluation of Norfloxacin tablets after oral administration in human.
Abstract: This article demonstrated development of
controlled release system of an NSAID drug, Diclofenac
sodium employing different ratios of Ethyl cellulose.
Diclofenac sodium and ethyl cellulose in different proportions
were processed by microencapsulation based on phase
separation technique to formulate microcapsules. The
prepared microcapsules were then compressed into tablets to
obtain controlled release oral formulations. In-vitro evaluation
was performed by dissolution test of each preparation was
conducted in 900 ml of phosphate buffer solution of pH 7.2
maintained at 37 ± 0.5 °C and stirred at 50 rpm. At predetermined
time intervals (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12,
16, 20 and 24 hrs). The drug concentration in the collected
samples was determined by UV spectrophotometer at 276 nm.
The physical characteristics of diclofenac sodium
microcapsules were according to accepted range. These were
off-white, free flowing and spherical in shape. The release
profile of diclofenac sodium from microcapsules was found to
be directly proportional to the proportion of ethylcellulose and
coat thickness. The in-vitro release pattern showed that with
ratio of 1:1 and 1:2 (drug: polymer), the percentage release of
drug at first hour was 16.91 and 11.52 %, respectively as
compared to 1:3 which is only 6.87 % with in this time. The
release mechanism followed higuchi model for its release
pattern. Tablet Formulation (F2) of present study was found
comparable in release profile the marketed brand Phlogin-SR,
microcapsules showed an extended release beyond 24 h.
Further, a good correlation was found between drug release
and proportion of ethylcellulose in the microcapsules.
Microencapsulation based on coacervation found as good
technique to control release of diclofenac sodium for making
the controlled release formulations.
Abstract: The objective of this manuscript is to find area under the plasma concentration- time curve (AUC) for multiple doses of salbutamol sulphate sustained release tablets (Ventolin® oral tablets SR 8 mg, GSK, Pakistan) in the group of 18 healthy adults by using computational mathematics techniques. Following the administration of 4 doses of Ventolin® tablets 12 hourly to 24 healthy human subjects and bioanalysis of obtained plasma samples, plasma drug concentration-time profile was constructed. AUC, an important pharmacokinetic parameter, was measured using integrated equation of multiple oral dose regimens. The approximated AUC was also calculated by using computational mathematics techniques such as repeated rectangular, repeated trapezium and repeated Simpson's rule and compared with exact value of AUC calculated by using integrated equation of multiple oral dose regimens to find best computational mathematics method that gives AUC values closest to exact. The exact values of AUC for four consecutive doses of Ventolin® oral tablets were 150.5819473, 157.8131756, 164.4178231 and 162.78 ng.h/ml while the closest values approximated AUC values were 149.245962, 157.336171, 164.2585768 and 162.289224 ng.h/ml, respectively as found by repeated rectangular rule. The errors in the approximated values of AUC were negligible. It is concluded that all computational tools approximated values of AUC accurately but the repeated rectangular rule gives slightly better approximated values of AUC as compared to repeated trapezium and repeated Simpson's rules.
Abstract: This study describes the methodology for the development of a validated in-vitro in-vivo correlation (IVIVC) for metoprolol tartrate modified release dosage forms with distinctive release rate characteristics. Modified release dosage forms were formulated by microencapsulation of metoprolol tartrate into different amounts of ethylcellulose by non-solvent addition technique. Then in-vitro and in-vivo studies were conducted to develop and validate level A IVIVC for metoprolol tartrate. The values of regression co-efficient (R2-values) for IVIVC of T2 and T3 formulations were not significantly (p