This report provides chemistry of salbutamol sulphate, tramadol hydrochloride, diclofenac sodium and ethylcellulose, physics of drug release through particle wall and use of microparticles in life sciences. Microparticles of salbutamol sulphate were prepared by using three different microencapsulation techniques i.e. coacervation thermal change, solvent evaporation and coacervation non-solvent addition by adjusting the ratio of drug to ethylcellulose. Salbutamol sulphate microparticles were compared with the microparticles of diclofenac sodium and tramadol hydrochloride and characterized by micromeritics, SEM, FTIR, X-RD, dissolution and thermal studies. The microcapsules were then compressed into tablets to study the variation of drug release between microcapsules and tabletted microcapsules. In vitro release profiles of prepared microcapsules and tabletted microcapsules were studied using USP XXIV dissolution apparatus I and II, respectively, in 450 ml double distilled water at 50 rpm maintained at 37°C. Microparticles were whitish, irregular in morphology and aggregated with good stability, fine rheological properties and excellent encapsulation efficiency. Percentage yield was almost greater than 90% in each batch. Initial burst effect was observed in the release pattern of tramadol hydrochloride and salbutamol sulphate formulations. No strong chemical interaction was observed between the drugs and polymer in microparticles. The release of drug from their respective formulations was sustained in the following rank: diclofenac sodium > salbutamol sulphate > tramadol hydrochloride. Polymer concentration and sustained release behavior were found to be directly proportional to each other. A slight increase in actual drug loading but profound increase in mean diameter of microcapsules was observed with an increase in the viscosity of ethylcellulose. The rate of drug release from microparticles decreased as the concentration of 2Abstract polyisobutylene was increased from 6% to 12% during microencapsulation. UV and FTIR spectroscopy, x-ray diffractometry and thermal analysis showed that ethylcellulose did not interact with these drugs. The release pattern of tabletted microparticles was affected significantly (p <0.05) by the addition of HPMC as excepient and insignificantly (p >0.05) by the type of dissolution media and stirring speed. All the batches of tablets showed good stability and reproducibility. Release profiles were evaluated by model-dependent and model independent approaches. The drug release from all the formulations was best explained by Higuchi’s equation, as the plots showed highest linearity, followed by zero order and first order. The mechanism of drug release was anomalous diffusion from all formulations. Non- solvent addition phase separation was found to be a suitable method to develop ethylcellulose based multi-unit controlled release drug delivery system. A sensitive reverse phase-high performance liquid chromatography (RP-HPLC) method with fluorescent detector (FLD) was developed and optimized for salbutamol sulfate determination in human plasma. In this regard, mobile phase specifications, extraction procedures, excitation and emission wavelengths were optimized. The HPLC system consisted of a Lichrosorb RP-C18 analytical column (4.6 × 200 mm, 5 μm) with FLD operated at excitation 228 nm and emission 310 nm. Mobile phase {CH 3 OH / (NH 4 )H 2 PO 4 (67 mM)(pH 3.0) / Triethylamine (TEA), 50 / 50 / 0.02 (v/v/v%)} was run at a flow rate of 0.7 mL/min. To clean up samples, a liquid-liquid extraction (LLE) procedure was selected and optimized. Salbutamol sulphate and tramadol hydrochloride eluted at 4.1 and 5.2 minutes respectively. Adequate extraction efficiency was achieved by DEHP (75.88-85.52%). The standard curve was linear for the range tested (0.5–80 ng/mL) and the coefficient of determination was 0.9989. A detection limit of 0.17 ng/mL was achieved. The intra- and inter-day 3Abstract precision was less than 4%. The present assay combines adequate accuracy and precision with sensitivity for salbutamol sulphate determination in human plasma and can be applied to study pharmacokinetics of salbutamol sulphate sustained release tablets after oral administration in human. A good linear correlation (R 2 = 0.9224, 0.945, 0.9363 and 0.9694 for T 1 , T 2 , T 3 and reference formulations, respectively) was obtained between the percent cumulative drug released (in vitro) and the percent cumulative drug absorbed (in vivo) data of these formulations at specific time points to develop level A in vitro-in vivo correlation that shows a reliable prediction of the plasma concentrations obtained following a single dose. Keywords: Coacervation, Solvent evaporation, Viscosity grade, Salbutamol sulphate, Tramadol hydrochloride, Dissolution, Diclofenac sodium, Ethylcellulose, Characterization, Method optimization, RP-HPLC method, Fluorescent detection, Ion-pair extraction, Calibration curve, Internal standard, In-vitro and in-vivo correlation.