Extrusion-spheronization Technique Research Articles

Design of Pistacia lentiscus (mastic gum) controlled release spheroids and investigating the influence of roll compaction

A gum isolated from Pistacia lentiscus of Pistacia genus was used as a release modifier in the preparation of diclofenac sodium spheroids, using the extrusion–spheronization technique. Spheroids prepared were formulated using diclofenac sodium, mastic gum (2.5–15%) and microcrystalline cellulose. Here, variables were studied and spheroids were characterized for average size, surface morphology, friability, bulk density and flow properties. In vitro drug release profile indicated an increase in drug release retardation with increasing mastic gum concentration. The formulated spheroids were stable with respect to their physicochemical characters and drug content over a period of 60 days at different temperatures and relative humidity. The objective of this study was to evaluate the influence of roll compaction and tableting on release of diclofenac sodium. Tablets prepared at different compression force played a key role in the dissolution of drug. Finally, the sustained release properties of spheroids were also maintained after compression.

Pelletization by Extrusion Spheronization Technique: An Excipient Review

Pellets/spheres have gained wide popularity amongst solid dosage forms due to numerous advantages offered by their spheroid nature and each pellet acting as a seperate drug delivery device. At an industrial scale, pellets are manufactured by extrusion-spheronization technique (ES) however, alternative techniques are also available. Such pellets obtained may be used as neutral or drug loaded pellets. Till date, microcrystalline cellulose (MCC) was considered as a golden standard for ES. Prior to MCC, sugar pareils were used as inert cores for drug loading. But due to physicochemical interactions of MCC, and technological difficulties faced during processing of MCC and sugar pellets, the need for the search of newer excipients as a pelletization aid has been triggered. To name a few, chitosan, carrageenan, starch, pectin, talc etc are being explored. The present review is an attempt to take account of the excipients used to design multiple unit particulate systems (MUPS) by ES technique and propose prospective excipient combinations to overcome limitations of existing pellets and excipients thereof. Keywords: Excipients, extrusion-spheronization, microcrystalline cellulose, pellets, pelletization techniques, prospective excipients.

Pelletization by Extrusion Spheronization Technique: An Excipient Review

Pellets/spheres have gained wide popularity amongst solid dosage forms due to numerous advantages offered by their spheroid nature and each pellet acting as a seperate drug delivery device. At an industrial scale, pellets are manufactured by extrusion-spheronization technique (ES) however, alternative techniques are also available. Such pellets obtained may be used as neutral or drug loaded pellets. Till date, microcrystalline cellulose (MCC) was considered as a golden standard for ES. Prior to MCC, sugar pareils were used as inert cores for drug loading. But due to physicochemical interactions of MCC, and technological difficulties faced during processing of MCC and sugar pellets, the need for the search of newer excipients as a pelletization aid has been triggered. To name a few, chitosan, carrageenan, starch, pectin, talc etc are being explored. The present review is an attempt to take account of the excipients used to design multiple unit particulate systems (MUPS) by ES technique and propose prospective excipient combinations to overcome limitations of existing pellets and excipients thereof. Keywords: Excipients, extrusion-spheronization, microcrystalline cellulose, pellets, pelletization techniques, prospective excipients.

Quantification of Mass Transfer During Spheronisation

Spherical granules (pellets) are quite useful in many pharmaceutical applications. The extrusion spheronisation technique is well established as a method of producing pellets of a spherical shape and narrow size distribution. After the extrusion, the cylindrical extrudates are transformed to spherical pellets by spheronisation. The frequently used models consider deformation and breakage during this process. However, the adhesion of fine particles has been neglected as a mechanism in spheronisation for many years. This study quantifies the mass transfer between pellets during spheronisation. During the investigation, the pelletisation aids (microcrystalline cellulose and kappa-carrageenan), the drug (acetaminophen and ibuprofen) and water content were varied systematically. A novel parameter, namely, the "mass transfer fraction" (MTF), was defined to quantify the mass transfer between the pellets. All four investigated formulations had an MTF between 0.10 and 0.52 that implies that up to 50% of the final pellet weight was involved in mass transfer. Both pelletisation aids showed similar MTF, independent of the drug used. Furthermore, an increase of the MTF, with respect to an increase of the water content, was found for microcrystalline cellulose formulations. In conclusion, the mass transfer between the pellets has to be considered as a mechanism for spheronisation.

Sustained-release alginate-chitosan pellets prepared by melt pelletization technique

Context: Alginate-chitosan pellets prepared by extrusion-spheronization technique exhibited fast drug dissolution.Objective: This study aimed to design sustained-release alginate pellets through rapid in situ matrix coacervation by chitosan during dissolution.Methods: Pellets made of alginate with chitosan and/or calcium acetate were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed such reaction to occur only in dissolution phase.Results: Drug release was retarded in pH 2.2 medium when pellets were formulated with calcium acetate or chitosan till a change in medium pH to 6.8. The sustained-release characteristics of calcium alginate pellets were attributed to pellet dispersion and rapid cross-linking by soluble Ca2+ during dissolution. The slow drug release characteristics of alginate-chitosan pellets were attributed to polyelectrolyte complexation and pellet aggregation into swollen structures with reduced erosion. The drug release was, however, not retarded when both calcium acetate and chitosan coexisted in the same matrix as a result of chitosan shielding of Ca2+ to initiate alginate cross-linkages and rapid in situ solvation of calcium acetate induced fast pellet dispersion and chitosan losses from matrix.Conclusion: Similar to calcium alginate pellets, alginate-chitosan pellets demonstrated sustained drug release property though via different mechanisms. Combination of alginate, chitosan and calcium acetate in the same matrix nevertheless failed to retard drug release via complementary drug release pattern.

Dual coating of swellable and rupturable polymers on Glipizide loaded MCC pellets for pulsatile delivery: Formulation design and in vitro evaluation

This study is aimed to develop and evaluate time dependent rupturable multiparticulate pulsatile delivery system for Glipizide. Microcrystalline cellulose (MCC) based pellets containing Glipizide were prepared by extrusion–spheronization technique (Type I pellets). These were further coated with two consecutive layers, a swellable layer of hydroxypropylmethylcellulose (HPMC) and a rupturable layer of plasticized ethylcellulose (EC) with fluidized bed coating to yield Type II pellets. Drug release and water uptake studies were carried out on formulated pellets. SEM was used to monitor the pellets’ morphology and change on exposure to dissolution medium. Both types of pellets were evaluated for particle size, flow, friability, dissolution and content uniformity. Immediate release pattern was optimized for Type I pellets to achieve more than 80% drug release within 30 min. Type II pellets displayed burst release and a lag period of 6–8 h. After selection of appropriate proportions of these pellets (Type I and Type II), drug release studies were performed which showed a pulsatile dissolution profile with a lag-time of 6–8 h. Multiparticulate approach with a blend of the two types of pellets was successfully used to develop a pulsatile release product for Glipizide.

Controlled-Release Pelletized Dosage Forms Using the Extrusion-Spheronization Process

ABSTRACT − Pellets, which are multiple-unit dosage systems, have the several therapeutic advantages over single-unitdosage systems in oral drug delivery. This review focuses on the current status and explores extrusion-spheronization tech-nique with special attention to controlled-release application of pellets including coated pellets for delayed release for-mulations, coated pellets for colon delivery, coated pellets for sustained drug delivery, sustained-release matrix pellets,pellets compressed into tablets, bioadhesive pellets, floating pellets, and pelletization with solubilization techniques.Key words − Pellets, Multiparticulates, Modified- release, Pelletization, Solubilization Pelletization process is an agglomeration process that resultsin agglomerates of a narrow size distribution in the range of0.5-1.5 mm with a low intra-agglomerate porosity (about 10%)and the higher density compared to the granules. Pellets areproduced by pelletization process and these agglomerates havethe relatively spherical shape, low friability and free flowingproperties, which facilitate the handling of pellets in the man-ufacturing process. Pelletization process can prevent the seg-regation of co-agglomerated components, resulting in animprovement of the content uniformity. Pelletization processcan also avoid the dust formation resulting in an improvementof the process safety, as fine powders can cause dust explo-sions and respiratory health problems. Pellets are widely usedin multiparticulate systems and multiparticulate systems havethe several therapeutic advantages over single-unit dosage sys-tems in oral drug delivery. The low inter- and intra-subjectvariability can be achieved by multiparticulate systems becausemultiparticulates can pass through the pylorus immediately afteradministration. Moreover, less effect of food on drug absorp-tion and rather uniform gastric emptying time than single-unitdosage systems can be attainable in multiparticulate systems.Safety concerns due to dose dumping of drugs, which havenarrow therapeutic index, is minimized in multiparticulate sys-tems, and more foreseeable drug delivery in sustained releaseformulation is possible because the total drug dose is dividedover many units, not in a single-unit system. The small size ofmultiparticulates also enables them to be well dispersed alongthe gastrointestinal (GI) tract, enhancing drug absorption andreducing the irritant effect that single-unit systems may causeto the mucosal lining, especially if remained for an extendedtime at a specific site. The spherical pellets can be coated withrate-controlling polymers or compressed into tablets to achievedelayed-release, extended-release, and targeted-release profiles.Multiparticulate systems with different dose strengths can beobtained from the same batch of drug-loaded pellets withoutadditional formulation or process modification. Pellets withdifferent drugs or with different release profiles can be blendedand formulated in a single-unit dosage form such as capsule,which promotes the delivery of two or more chemically com-patible or incompatible drugs at the same or different sites inthe GI tract.Although several pelletization techniques such as high-shear,fluid-bed, spray-drying, and rotary-granulation techniques, aredeveloped and available in the pharmaceutical industry, theextrusion-spheronization technique has certain advantagessuch as preparation of spherical pellets with uniform size andhigh-drug loading (up to 90%) at a moderate cost using min-imum excipients. In various pelletization techniques, thisreview focuses on the current status and explores extrusion-spheronization technique with special attention to controlledrelease application of pellets. A thorough discussion of processvariables for extrusion-spheronization or characterization of

Formulation design and optimization of tastemasked mouth-dissolving tablets of Tramadol hydrochloride

The aim of the present study was to mask the extremely bitter taste of Tramadol HCL, an opioid analgesic, and to formulate a tablet which can rapidly disintegrate in saliva (rapidly disintegrating tablet). The crucial aspect in the formulation of mouth-dissolving tablets is to mask the bitter taste and to minimize the disintegration time. Taste masking was done using sweetening agent and D-mannitol and taste-masked pellets were prepared by extrusion spheronization technique. Prepared pellets were tested for drug content, taste evaluation in oral cavity and molecular property. Pellet shows significant taste masking, confirmed by in vitro taste evaluation; therefore, it was selected for further study. Pellets were evaluated for density, angle of repose, Carr’s index, Hausner’s ratio and sphericity while tablets were evaluated for disintegration and in vitro dissolution. A 32 full factorial design and statistical models were applied to optimize the effect of two factors, i.e. superdisintegrant sodium starch glycolate and taste-masking agent (D-mannitol). In this study, response surface methodology was used for designing of the experiment, generation of mathematical models and optimization study. Taste evaluation of pellets in human volunteers revealed considerable taste masking with a degree of bitterness below threshold value (2.0) within 10 s, whereas Tramadol HCl was rated intensely bitter with a score of +4 for 10 s. The size of the pellets varied from 0.895 to 1.423 mm for different batch and found to be a spherical. Disintegration time of different formulations varied from 30 to 60 s. It was observed that the responses, i.e. disintegration time and sphericity were affected by both the factors. The statistical models were validated and can be successfully used to prepare optimized taste-masked mouth-dissolving tablets of Tramadol HCl with adequate disintegration and shape. Key words: 32 factorial design, rapidly disintegrating tablet, response surface methodology, taste-masked granule, Tramadol HCL

Indomethacin sustained release pellets prepared by extrusion-spheronization

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release multiparticulate form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IM) sustained release pellets containing 5 or 10 % w/w of the drug were prepared using an extrusion-spheronization technique. Different concentrations of hydrophilic polymers, polyethylene glycol 4000 (PEG 4000), hydroxypropyl methylcellulose E5 LV premium (HPMC) and polyvinyl pyrrolidone (PVP K30), were mixed at different concentrations (5,10 and 20 %) with Avicel PH 101 to prepare the sustained release formulae. Moreover, a mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The resulting pellets were characterized for content, particle size, shape and dissolution profile. The studies on the effect of the polymers used on Avicel rheological properties revealed that the magnitude of torque for the system was decreasing as the polymer concentration increased. The in vitro release of IM from the prepared Avicel pellets was found to be dependent upon the type and concentration of the added polymer. The rank order of IM release in the presence of the investigated polymers was as follows: PEG > HPMC > PVP. Furthermore, the magnitude of IM release rate from the pellet formulations was found to be dependent on the magnitude of the peak torque of the pellet forming paste, which in turn depends on the type and concentration of the added polymer. Increasing IM loading from 5 to 10 % has led to an increase in dissolution rates. At least two of the prepared pellet formulations showed dissolution profiles similar to the commercial product Bonidon 75 SR capsules. In conclusion, the formulation of IM sustained release pellets successfully controlled the drug release which might be beneficial in lowering the risk of side effects and improving patient convenience as an advantage of the pellets as a drug delivery system.

Influence of operational variables in multi-particulate delayed release systems for colon-targeted drug delivery of celecoxib using extrusion spheronization

The present research was aimed to formulate and evaluate pH and time-dependent multiparticulate systems for colon-targeted drug delivery of celecoxib (CXB) with maximum drug absorption, reduced peak plasma fluctuations, and minimum potential side effects. Multiple unit delayed release systems of the drug in MCC (Avicel® PH-102) grade were prepared using polymethacrylate polymers (Eudragit® L-100 and RSPO) as a granulating binder by the extrusion- spheronization technique and characterized for their shape, size, size distribution, friability, density, and moisture content. In vitro release studies were performed in 0.1N HCl, for first 2 h then further performed in phosphate buffer (pH 6.8) for 24 h. The resulting pellets were prepared by extrusion spheronization using different grades of polymethacrylate polymers as a granulating binder, showing a substantial decrease in drug release in initial 5 h (16.28-16.7%) and releasing most of the drug in 12-24 h. The geometric and arithmetic mean diameter ranged from (490 to 780 μm) and (636 to 734 μm), respectively. The minimum to maximum range for circularity, elongation and rectangle were found to be (0.847±0.009 to0.965±0.078), (1.036±0.057 to 1.185±0.023), and (0.724±0.041 to 0.791±0.047) respectively showing the proper shape and size of the pellets. The content of CXB in the prepared pellets was observed between 98.70 and 99.47% justifying the uniform drug distribution. The in vitro dissolution studies showed that the retardant effect in initial 5 h and most of the drug release in 24 h depended on the ratio and concentration of different grades of methacrylate polymers used in the formulation. CXB-loaded MUPS prepared by the extrusion-spheronization technique using polymethacrylate polymers showed immense potential for colon-specific drug delivery of the drug.

Exploring the Potential of A Highly Compressible Microcrystalline Cellulose as Novel Tabletting Excipient in the Compaction of Extended-Release Coated Pellets Containing an Extremely Water-Soluble Model Drug

Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion-spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.

CHITOSAN SPHEROIDS WITH MICROWAVE MODULATED DRUG RELEASE

The interplay efiects of matrix formulations with mi- crowave on drug release were investigated using an agglomerate system. Chitosan spheroids were formulated with stearic acid and/or sodium chloride by extrusion-spheronization technique, and chlorpheniramine maleate as water-soluble model drug. The spheroids were treated by microwave at 80W for 5 to 40min. The proflles of drug dissolution, drug content, drug-polymer interaction, polymer-polymer interaction, sodium leaching, matrix morphology and integrity were determined. Unlike chitosan matrix prepared by ionotropic gelation method, the retardation of drug release from chitosan spheroids by microwave re- quired a more complex formulation containing both stearic acid and sodium chloride unless a high stearic acid fraction was used. These spheroids demonstrated a high resistance to disintegration during dis- solution owing to salt-induced bridging by sodium chloride. In response to microwave, sodium chloride aided stearic acid spread and efiected domain interaction via C = O moiety over a matrix with reduced spe- ciflc surface area thereby reducing drug dissolution. The drug release of spheroids can be retarded by microwave through promoting the lay- ering of hydrophobic stearic acid in a matrix structure sustained by sodium chloride.

Development andin vitroevaluation of enteric coated multiparticulate system for resistant tuberculosis

The multiparticulate formulation of sodium para aminosalicylate for oral administration was developed by extrusion spheronization technique. Microcrystalline cellulose was used as filler in concentration of 14.4% w/w. Pellets were coated with Eudragit L 30 D-55 using fluidized bed processor. Different weight gains of acrylic polymer were applied onto the pellets and evaluated for in vitro dissolution behavior in 0.1 N HCl for two hours and then media was changed to phosphate buffer pH 6.8. A 60% w/w coating level of Eudragit L30 D 55 has produced the most acceptable results against the gastric attack. 3% Seal coat of HPMC E5 was also applied in order to protect the drug from migration into the Eudragit coat and film coat was applied in order to prevent aggregation of pellets in the dissolution media. Morphological characteristics of developed pellets were also investigated by scanning electron microscopy and found to be smooth and spherical. Developed system was found to be suitable for the delivery of Sod PAS in to intestinal region.

Thermal treating as a tool to produce plastic pellets based on Eudragit RS PO and RL PO aimed for tableting

A 3 2 full-factorial design was used for preparation of pellets using extrusion–spheronization technique. Independent variables were %ibuprofen (40, 60, 80) and %Eudragit RS PO/RL PO (0, 50, 100). In all formulations 3% w/w PVP K30 and 10% Avicel PH101 were also used. The pellets were cured in oven at 60 °C for 24 h. The evaluated responses were crushing strength or yield point, elastic modulus and mean dissolution time (MDT) of pellets. The cured pellets were also compressed at 15 kN compaction force and then observed under scanning electron microscope. It was shown that the cured pellets containing 40% or 60% drug exhibited a plastic deformation without any fracture under mechanical tests. The curing process resulted in significant decrease in the elastic modulus of the pellets. The SEM of the compressed pellets were also confirmed the plastic behavior of these pellets. The transition of pellet behavior from brittle to plastic upon curing was due to shift of Eudragit structure from glassy to rubbery state which was supported by DSC studies. However pellets with 80% drug showed brittle properties even after curing due to presence of less amount of Eudragit in their structure. Increasing the ratio of Eudragit RS in the pellets decreased the yield point and elastic modulus of cured pellets containing 40% or 60% drug, indicating more plastic behavior of these pellets. This was attributed to lower Tg of Eudragit RS than Eudragit RL. The curing process also retarded drug release from pellets and increased MDT. Increasing the ratio of Eudragit RS in the pellets increased MDT in cured pellets containing 40% or 60% drug but had no effect in pellets with 80% drug. Overall the results of this study revealed that thermal treating is a proper tool to produce plastic ibuprofen pellets based on Eudragit RS PO and Eudragit RL PO.

Design and evaluation of pH sensitive multi-particulate systems for chronotherapeutic delivery of Diltiazem hydrochloride

A pH sensitive multi-particulate system intended to approximate the chronobiology of angina pectoris is proposed for colonic targeting. The system comprising of Eudragit S-100 coated pellets was designed for chronotherapeutic delivery of diltiazem hydrochloride. The drug loaded core pellets were produced by aqueous extrusion spheronization technique using microcrystalline cellulose as a spheronizing aid and PVP K 30 as a binder. Different coat weights of Eudragit S-100 were applied to the drug loaded pellets in an automatic coating machine to produce the pH sensitive coated pellets. Scanning electron microscopy revealed that the core pellets were discrete, spherical, or oval with a slightly rough surface whereas the coated pellets were covered with a uniform and continuous acrylic film. Optical microscopic image analysis portrayed that the values of aspect ratio and pellet circularity were close to 1.0, indicating the core pellets were almost spherical in shape. The friability with glass spheres was below 1.0%, signifying the core pellets produced were sufficiently hard. In vitro dissolution studies of the coated pellets performed following pH progression method showed that the drug release from the coated pellets depended on the coat weights applied and pH of the dissolution media. Since, diltiazem hydrochloride is a drug, which exhibits a high solubility, it would be possible to minimize drug release from the coated pellets below pH 7.0, and effectively release the drug at colonic pH only with higher coat loads (15-20% weight gain).

Development of Controlled Release Spheriods using Natural Polysaccharide as Release Modifier

A polysaccharide hydrogel was isolated from the seeds of Tamarindus indica (tamarind) and was used as release modifier for the preparation of diclofenac sodium spheroids, using extrusion-spheronization technique. The process was studied for the effect of variables to arrive at spheroids with satisfactory particle shape, size and size-distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density, and flow properties. The in vitro release studies exhibited a zero-order release kinetics that was confirmed by Higuchi's and Peppas' models. A credible correlation was obtained among swelling index, viscosity, surface roughness of the polysaccharide, and in vitro dissolution profile of the spheroids. In the comparative bioavailability study, we found that the developed spheroids were able to sustain the drug release over 8 hr and could improve the extent of absorption and bioavailability of the drug.

Eudragit NE40–Drug Mixed Coating System for Controlling Drug Release of Core Pellets

This study was aimed at developing a controlled-release coating system around core pellets with aqueous dispersion, along with some water channeling agents. Core pellets of diltiazem were prepared using the extrusion-spheronization technique and subsequently coated with aqueous dispersion of Eudragit NE40 alone, or drug–polymer mixtures using bottom-spray fluidized bed coater. The lag time in drug release profiles increased as the coating levels of Eudragit NE40 were increased, whereas no lag time was observed in core pellets coated with drug–polymer mixtures. Mixed coating at the 7% level exhibited comparatively better release profiles and provided desirable release rates during the 12-hour testing interval. Diltiazem HCl release from mixed coating was fairly independent of pH and drug loading. Curing of coated pellets was found to be an essential step for stable drug release profiles. The selection of core size range had remarkable effect on drug release rate and was considerably reduced by using greater core size.

Physicochemical properties of granulating liquids and their influence on microcrystalline cellulose pellets obtained by extrusion-spheronisation technology

The use of ethanol or ethanol/water mixtures as granulation liquids in the extrusion-spheronisation process results in the formation of pellets with significantly different mechanical and structural properties from those prepared using water alone. The product of surface tension ( γ L), relative permittivity ( ɛ R) of the granulation liquid and the cosine of contact angle ( Θ) of granulation liquid on pellets solid has been introduced in order to explain the mechanism of this phenomenon. A correlation is shown between the factor γ L × cos( Θ) × ɛ R and the properties of the pellets produced. We have introduced the γ L × cos( Θ) × ɛ R which can be considered to represent the driving and counteracting forces of pellet contraction during drying. The contact angles and surface tensions were evaluated using the Wilhelmy plate method. Pellets were produced by extrusion-spheronisation technique using water, ethanol and ethanol/water mixtures as granulation liquids. Subsequent characterization of the pellets showed that their tensile strength and disintegration times increase with increase in the proposed factor γ L × cos( Θ) × ɛ R, while friability, average pore diameter and porosity decreases. The observed correlations show, that the granulation liquid influences the mechanical and structural properties of the pellets through the contraction driving and contraction counteracting forces during drying.

On-line monitoring of moisture content in an instrumented fluidized bed granulator with a multi-channel NIR moisture sensor

The applicability of a near-infrared reflectance spectroscopic method was tested. The set-up used was constructed for the determination of water during different unit operations performed in a fluidized bed granulator. The granulation of three different formulations and the drying of one pellet formulation were investigated. The pellets were prepared by the continuous extrusion spheronisation technique. It proved possible to measure the moisture content of granules with a standard error of performance of 0.2%. The reference method used was based on the measurement of loss on drying (infrared dryer, wet basis). The applicability of the near-infrared method in pharmaceutical formulation and process development work was investigated using different liquid flow rates and drying end points. Combining the continuous measurement of moisture content and the product temperature measurement creates a novel tool for observing both the granule spraying and the drying phase. Different moisture profiles of the granules were clearly distinguished as well as the different drying end points.

Use of Colloidal Silica as a Separating Agent in Film Forming Processes Performed with Aqueous Dispersion of Acrylic Resins

AbstractAqueous dispersion of polymers are going to take the place of the corresponding organic solution in the film forming process of tablets, pellets and granules, because of some definite advantages.Among the additives used in formulation techniques, talc, that is normally utilized as an antiadherent and polishing agent, presents some problems connected with its tendency to form sedimentation. For this reason, during the film coating operation, the dispersion must be always kept under constant and proper agitation, however, the danger of blocking the piping and the spraying system of the equipment employed cannot be completely avoided.On the bases of these observations, the aim of this research work is to evaluate the possibility of substituting talc with colloidal silica as separating agent in aqueous dispersion of film acrylic resins, normally used in the preparation of prolonged release systems.Results concerning fluid bed coating processes of pellets prepared by extrusion-spheronization technique ...