M. Jacob

Development of spray-dried acetaminophen microparticles using experimental designs

Experimental factorial designs were built to investigate the effects of five parameters on production yields and moisture contents of spray-dried products. These factors concerned both the solution feed (drug concentration, colloidal silica concentration and polymer/drug ratio) and the spray dryer (inlet temperature and feed rate). Three formulations containing cellulose derivatives and acetaminophen were tested. The aim of the study was to optimize the operating conditions to maximize production yields while minimizing moisture contents. First screening experiments consisting of fractional factorial designs revealed the most significant factors to be inlet temperature, feed rate and their interaction for both formulations containing sodium carboxymethylcellulose and feed rate and colloidal silica concentration for the formulation containing microcrystalline cellulose. Then, the optimal operating conditions were estimated by response surface methodology. Central rotational composite designs showed quadratic models were adequate. New assays were carried out using these last conditions to evaluate both the repeatability and reproducibility of the spray-drying technique. Yields above 80% and moisture content of approximately 1% were reached. The characterization of microparticles revealed the poor flowability of the spray-dried products due to significant cohesiveness and very small size (less than 55 microm).

Factorial design in the feasibility of producing Microcel MC 101 pellets by extrusion/spheronization

Abstract This study evaluates the effects of certain process variables in the feasibility of producing Microcel MC 101 pellets by the extrusion/spheronization technique. A 2 3 factorial design was realised to demonstrate the influence of the significant factors and their interactions in the experimental response. The selected process variables such as water content, extruder screen size and spheronizer speed were studied, as well as their influences on the properties of particle size distribution and the densities were determined. The results showed that high levels of the three factors increased sphere size, and low levels decreased it. A strong interaction between water content and extruder screen size is observed for the particle size distribution response. Extruder screen size has a significant effect on the bulk density. Water content and spheronizer speed interaction influence the sphere density.

Preparation of proteolytic enzyme extracts from Ananas comosus L., Merr. fruit juice using semipermeable membrane, ammonium sulfate extraction, centrifugation and freeze-drying processes

Crude purified bromelain extracts were obtained from 0.26% protein pineapple juice using sequential batch membrane processing systems which included microfiltration (MF) and ultrafiltration (UF) followed by ammonium sulfate extraction, ultracentrifugation and freeze drying. The membrane treatments (with an 8 μm mineral MF and a 10000 molecular weight cut-off (MWCO) organic UF membranes), combined with 60% ammonium sulfate extraction resulted in 0.75–0.8% protein concentration, with 99% protein rejection. A 70% ammonium saturation and ultracentrifugation process (27 000 × g at 2–3 ° C), prior to freeze drying, were used in the last step to remove the residual non-protein constituents. These processes achieved low-moisture freeze-dried, and light-colored extracts, free of non-protein constituents and which accounted for about 50% yielded extracts containing 98% protein. The extracts assayed for bromelain and proteolytic activity resulted in almost 100% potential recovered, at completion. However, bromelain and proteolytic activity decay during the processes described above is essentially caused by losses through adsorption on the UF membrane relative to the level of concentration reached.

Physico-chemical characterization and tabletting properties of Scleroglucan

Abstract The aim of this work was to describe those characteristics of scleroglucan that are relebant to its employment as a sustained release agent in hydrophilic swellable matrices. Besides a brief review of the rheological properties of scleroglucan, various measurements have been effected to define the physical and mechanical properties of scleroglucan and to forecast its behavior as a matrix carrier.

A Process to Produce Effervescent Tablets: Fluidized Bed Dryer Melt Granulation

The purpose of the present study was to apply melt granulation in a fluidized bed dryer (fluidized bed dryer melt granulation) to manufacture one-step effervescent granules composed of anhydrous citric acid and sodium bicarbonate to make tablets. This study permitted us to establish that such process parameters as concentrations of polyethylene glycol (PEG) 6000, residence times in the fluidized bed dryer, fineness of PEG6000, fineness of initial mixture effervescent systems, and efficiency of two lubricants markedly affect some granule and tablet characteristics. It is a dry process that is simple, rapid, effective, economical, reproducible, and particularly adapted to produce effervescent granules that are easily compressed into effervescent tablets.

Natural Polymer Hydrophilic Matrix: Influencing Drug Release Factors

In porous hydrophilic polymeric systems, two phenomena control the release of drugs: the water uptake and polymer swelling.Directly compressed hydrophilic matrices were prepared with scleroglucan as gelling agent. A principal components analysis enables the authors to study the correlation between the above phenomena and the dissolution behavior in order to interpret the effect of polymer concentration, excipient solubility and compression force on the drug release.

The rheology of wet powders: A measuring instrument, the compresso-rheometer

In order to control the mechanical properties and granulation processes of wet powders, steps were taken to design and develop a measuring instrument, the compresso-rheometer. Initial experiments were carried out on binary associations between microcrystalline cellulose powder and varying quantities of water.

Effects of Cellulose Derivatives and Additives in the Spray-Drying Preparation of Acetaminophen Delivery Systems

Microcrystalline cellulose (MCC), sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and ethylcellulose (EC) were used for the production of time-controlled acetaminophen delivery systems using a spray-drying technique. The influence of factors such as polymer concentration, inlet temperature, and drug/polymer ratio were investigated. The product yields were a function of the type and concentration of the polymer, with the highest values being reached from feeds containing 1% MCC and EC. Parameters of 1% polymer concentration and an inlet temperature of 140 degrees C gave rise to optimal processing conditions. Using these parameters, the influence of some adjuncts, such as polyethylene glycol 6000 (PEG 6000), dibutyl sebacate (DBS), polyvinylpyrrolidone (PVP), and carboxylic acids such as citric acid (CA), phthalic acid (PA), succinic acid (SA), tartaric acid (TA), and oxalic acid (OA), on the spray-drying process was evaluated. Of the additives tested, PVP (with MCC), DBS (with EC), and PEG 6000 (with NaCMC) induced yield decreases from 70% to 49%, 66% to 39%, and 37% to 17%, respectively. As for carboxylic acids (with NaCMC), similar or better performances of 43%, 45%, 47%, and 49% were obtained with SA, OA, PA, and TA, respectively. Dissolution studies in pH 1 dilute HCl and pH 6.8 phosphate buffer dissolution media showed that formulations consisting of 1% polymer with a drug/polymer ratio of 1/1 exhibited the slowest drug release, with the spheroids coated with NaCMC and HEC showing the longest T50% values (with 45 and 53 min at pH 1 and 49 and 55 min at pH 6.8, respectively). Slightly better sustained drug release in pH 6.8 dissolution medium was reached, showing the following trend: HEC > NaCMC > MCC > EC > HPMC. Concerning the additives, the trends in dissolution T50% of drug revealed TA > SA > CA > OA > PVP > PA > DBS in acidic pH 1 dissolution medium and PVP > OA > TA > SA > PA > CA > DBS in phosphate buffer at pH 6.8.

Permeability to hydrogen ions of an enteric coating polymer and interaction of film formulation factors

The influence of cellulose acetate phthalate film formulation on permeability to hydrogen ions was studied by measuring the permeability coefficients of free films in a diffusion cell. The effect of the studied factors and the interaction among them have been found to be significant. Aqueous and organic films have distinct behaviour; the former are considerably more permeable. Swelling experiments, X-ray diffraction and differential scanning calorimetry studies were carried out to clarify the differences observed in the permeability of the films.

pH influence on the stability of ascorbic acid spray-drying solutions

Abstract The profile of the degradation rate of ascorbic acid from unbuffered solutions has been determined for pH range 2.5–5.0 at 20°C ± 0.5° C. The rate of oxidation was pH dependent, showing a maximum at pH 4.0 and a minimum at pH 2.5 to 3.0. Regression analysis and analysis of residues revealed zero-order kinetics at all values of pH at specific wavelengths to each pH, and to pH 2.5 measured at the isosbestic point (250 nm). This last wavelength cannot be used in kinetic determination.