Kollidon CL Research Articles

Development of ibuprofen tablet with polyethylene oxide using fused deposition modeling 3D-printing coupled with hot-melt extrusion

Ibuprofen is known to plasticize several polymers used in hot-melt extrusion, and it is considered challenging to achieve immediate release for ibuprofen using fused deposition modeling. Therefore, this study aimed to print ibuprofen tablets with a focus on achieving rapid release. Polyethylene oxide (Polyox WSR N80) was used as the main matrix to form the ibuprofen filament, because of its water-soluble properties and ability to manifest suitable mechanical properties, even with high drug loading (40% w/w). Several release modifiers, such as Kollidon VA64, Kollidon 12PF, Kollicoat IR, Kollidon CL, and mannitol, were added separately to the formulation, following which their effects on enhancing the drug release rate were investigated. Their effects on the mechanical properties of the filaments have also been assessed in this study. It was demonstrated that adding soluble Kollidon grades, such as Kollidon VA64 and Kollidon 12PF, enhanced the drug release rate. In addition, the tablet design with a high surface-to-mass ratio was beneficial for increasing the drug release rate. However, incorporation of the release modifiers discussed above decreased the flexural modulus of the filament. Additionally, it is important to tailor the printing parameters by considering the properties of the filament, to acquire good quality printlets. The tablet consisting of 30% ibuprofen and 20% Kollidon VA64 at the highest dose used in this study (84 mg) released 80% of the drug, in approximately 90 min. To further increase the release rate and drug dose, other additives, such as viscosity-increasing agents and reinforcing additives, can be explored. This study shows the potential of fabricating ibuprofen tablets with rapid release characteristics using Polyox WSR N80, via fused deposition modeling 3D-printing.

The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment

Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet.

Formulation and Optimization of Atovaquone Micronized Suspension by Top-down Method

Abstract: Aim: The present work aimed to tackle the solubility issue of a Biopharmaceutics Classification System (BCS) II drug, Atovaquone. Methods: Formulation of micronized suspension of atovaquone was optimized by employing a 32 full factorial design keeping poloxamer 188 (wetting agent) and phospholipon 90H (stabilizer) as the influential variables affecting the dependent variables viz. particle size and polydispersity index (PdI). Selected formulations from the optimized design space were further evaluated for dissolution and the formulation exhibiting maximum dissolution within 120 min was selected. The optimized batch consisting of atovaquone (15%), poloxamer 188 (2%), phospholipon 90H (1%), glycerin (10%) in the aqueous vehicle was microfluidized. Results: The particle size of resultant suspension was Zavg = 1313 ± 40 nm and PdI =0.1± 0.05. The zeta potential of the final micronized suspension was 0.0555 mV which indicated steric stabilization of the particles. The micronized suspension was adsorbed on a mixture of Kollidon CL SF and Aerosil 200 (2:1) and then dried and passed through 40# sieve. Conclusion: The solid-state characterization of the formulation revealed that the crystalline nature of the drug was retained after the milling process. The saturation solubility and in-vitro dissolution of adsorbed micronized suspension were 2.3-fold times enhanced as compared to the pure drug suspension due to a reduction in particle size. The top-down approach can be employed to improve the poor aqueous solubility of atovaquone. Key words: Atovaquone, Micronized suspension, Microfluidization, Full factorial design, Solubility enhancement.

Formulation and study of nebivolol containing orodispersable tablets

Abstract In case of chronic diseases patient compliance to long-term treatment is of utmost importance. Patient compliance is generally higher for pharmaceutical forms dispersing in the oral cavity. One classic example for long-term therapy is hypertension. The aim of this study is to obtain nebivolol hydrochloride containing orally disintegrating tablets. As manufacturing technology, direct compression was chosen and rapid disintegration was aimed to be achieved using superdisintegrants. Various formulae have been developed, containing Kollidon and Polyplasdone in different concentrations, and the obtained dry powder mixtures were studied for their rheological properties. Afterwards these mixtures were compressed to obtain tablets. Active ingredient was embedded in the formulations with the shortest disintegration times (15 and 18 seconds) and the obtained tablets were studied for disintegration time, mechanical resistance, drug content and dissolution. Our results show that the pharmaceutical formulations containing Kollidon CL 5% or Polyplasdone XL 3% fulfill the requirements of orally disintegrating tablets, having a disintegration time under 3 minutes, proper mechanical resistance (greater than 80N) and the dissolution of the active ingredient is greater than 80% in 30 minutes.

Structure-Properties Relationship in the Evaluation of Alginic Acid Functionality for Tableting.

The aim of this study is to investigate the relationship between the structural, molecular, and particulate properties of alginic acid and its functional characteristics in direct compression (tabletability, compressibility, elasticity, deformation mechanism, and disintegration ability). Therefore, accurate characterization of two different batches of alginic acid was executed (X-ray powder diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electronic microscopy, 1H nuclear magnetic resonance, size exclusion chromatography - multi angle light scattering, viscosimetry, carboxylic acid titration, powder flowability, true density, laser granulometry). Results showed that molecular weight seems to affect tablet properties and that the alginic acid with the lowest molecular weight provides the hardest tablets with the lowest elastic recovery. Furthermore, these results show the potential interest of exploiting alginic acid as filler excipient in tablet formulation. Finally, disintegration properties of tested materials were found to be close to that of commercial superdisintegrants (Glycolys® and Kollidon Cl®) but not correlated to their swelling force. It can be concluded, for the first time, that the determination of alginic acid molecular weight seems key for applications in direct compression and in particular for obtaining tablets with reproducible strength.

Experimental design approach for development of novel microemulsion system and immediate release self microemulsifying tablet of nebivolol HCl

The objective of this study was to determine specific combination of pharmaceutical excipients that lead to formulation of efficient nebivolol hydrochloride SMEDDS and its subsequent formulation into IR-SET (Immediate release- Self emulsifying tablet) which will enhance its solubility and dissolution. Solubility and Pseudo-ternary phase studies were carried out to identify the excipients showing highest solubility and to identify the zone of microemulsion with selected ingredients. Liquid-SMEDDS (L-SMEDDS) were optimized for Concentration of oil(X1) and Smix(X2) and formulated using a combination of Kollisolv GTA as oil, Tween 80 as surfactant and propylene glycol as co-surfactant which gave smaller droplet size(Y1) 55.98nm , Emulsification time (Y2) 16±1.5 s,% transmittance (Y3) 99.94±0.47%. Neusilin US2 was used as solid carrier for solidification of L-SMEDDS in to Solid-SMEDDS (S-SMEDDS) by adsorption technique. IR-SET of nebivolol were formulated with S-SMEDDS and optimized for the concentration of binder (X1) (PVP K30) and superdisintegrant (X2) (KOLLIDON CL) which showed low Disintegration time (Y1) (92±0.5s) and low Friability(Y2)(0.424±0.03%). Also the DSC and XRD data revealed the molecular state of the drug in S-SMEDDS. The extent of in-vivo drug release and ex-vivo diffusion values from L-SMEDDS and IR-SET was much higher than pure drug and marketed tablet. In conclusion, the results showed potential of SMEDDS to improve solubility and thus the bioavailability.

FORMULATION AND EVALUATION OF SOLID DISPERSION INCORPORATED FAST DISINTEGRATING TABLETS OF TENOXICAM USING DESIGN OF EXPERIMENT

The aim of the present work is to develop fast dissolving tablets from the solid dispersion of Tenoxicam for enhancement of solubility. The solid dispersions of Tenoxicam were prepared with Kollidon CL, PVP K30 and Poloxamer 127, in 1:1:1, 1:2:1 and 1:3:1 by using solvent evaporation method. The prepared solid dispersions were analyzed for all the physical parameters, drug: carrier interactions like FTIR, SEM, XRD. Solid dispersions showed a better dissolution compared to the pure drugs and among all the other formulations SD9 shows high percentage drug release i.e. 99.11 ± 5.17% for 90 min and selected as an optimized formulation for the preparation of fast disintegrating tablets of Tenoxicam. Gellan Gum, Fenugreek Seed Mucilage and L-HPC (low, middle and high concentrations) used in the preparation of fast disintegrating tablets prepared by direct compression method using 33 Response surface method. The post compression parameters of all the prepared tablets were within the limits. TF13 was selected as optimized formulation based on its highest disintegration time 36 sec and drug release 99.68 ± 1.52% for 10 min. Drug-excipients characterization also revealed that there is no interaction. Hence it concluded that solid dispersions incorporated fast disintegrating tablets is very useful approach for immediate release of Tenoxicam in the efficient management of inflammation and pain.

FORMULA OPTIMIZATION OF ORALLY DISINTEGRATING TABLET CONTAINING MELOXICAM NANOPARTICLES

Meloxicam is one of oxicams anti-inflamatory drugs that are effective to relieve toothaches, arthritis, dysmenorrhea, and fever. Meloxicam in this study was milled with High Energy Milling (HEM) method to obtain its nano size and then direct compression method was used to produce Orally Disintegrating Tablet (ODT). ODT is designed to be rapidly dissolved on the tongue within a minute. It can be administered without water or chewing and may improve the bioavailability and effectiveness of the drug, and increase the patient’s adherence. The present study aimed to understand the effects of Ac-Di-Sol and Kollidon CL as superdisintegrants, that were used separately or in combination, on the characteristics of nanoparticles meloxicam ODT. It was also to obtain the best proportion of combination between Ac-Di-Sol and Kollidon CL that can produce the optimum formula of meloxicam ODT. The effects of single or combined superdisintegrants were evaluated using Simplex Lattice Design (SLD). Ac-Di-Sol (X 1 ) and Kollidon CL (X 2 ) were the independent variables, while the dependent variables were friability (Y 1 ), disintegrating time (Y 2 ), wetting time (Y 3 ), and percent meloxicam release after 60 seconds (Y 4 ). Optimization of five nanoparticle meloxicam ODT formulas was conducted using Design Expert 7.1.5. The combination of Ac-Di-Sol 4.05mg (X 1 ) and Kollidon CL 10.95mg (X 2 ) in 150mg nanoparticles meloxicam ODT can produce optimal ODT characteristics. After verification there was no difference between predicted value and observed value with p value > 0.05.

The application of povidone in the preparation of modified release tablets

Abstract The aim of the study was to investigate the modified release of a model substance, of tablets containing different types of Kollidon and particular additives. Additionally, the release kinetics and mechanism of prolonged release of certain tablet preparations were investigated. In this work, tablets containing different types of povidone (Kollidon CL, Kollidon 30, Kollidon SR and other excipients) were prepared by the direct compression technique. The results showed that tablets with fast disintegration and release should contain in their composition, Kollidon CL, lactose and Avicel, however, the use of β-CD instead of lactose or Avicel brings about a slight prolongation in the disintegration time of tablets and the release of an active substance. Furthermore, while other tablet compositions generated within this study must be considered as being prolonged release types, only two of these showed the best fitted mathematical models. The in vitro dissolution data reveal that the dissolution profiles of the two formulations, one containing Kollidon SR with the addition of Kollidon 30, and the second with HPMC K15M, Kollidon 30, Kollidon CL and lactose, best fitted the Higuchi model. Moreover, the release mechanism of these two formulations plotted well into Korsmeyer-Peppas, indicating a coupling of drug diffusion in the hydrated matrix, as well as polymer relaxation – the so-called anomalous transport (non-Fickian).

Formulation and evaluation of taste mask pellets of granisetron hydrochloride as oro dispersible tablet

Orally disintegrating systems have carved a niche amongst the oral drug delivery systems due to the highest compliance of the patients, especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to withstand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. The purpose of this research was to mask the bitter taste of granisetron hydrochloride. To mask the taste Kollicoat(r) Smartseal 30D was used as coating polymer for pellet coating. The coated pellets of the drug was directly compressed with different superdisintegrant as AC-Di-Sol, Explotab and Kollidon CL in different concentration 5.0-7.5% w/w into an ODT. The prepared tablets were evaluated for hardness, friability, weight variation, wetting time, wet absorption ratio, in-vitro disintegration time and in vitro dissolution studies. Tablets exhibited quick disintegration characteristics with Kollidon CL in concentration 7.5% w/w i.e., within 20 seconds, which is characteristic of orally disintegrating dosage forms. More than 98% of drug was released from the formulations within 15 minutes. Formulations subjected to stability testing as per the ICH guidelines for 3 months, indicated stability with no change in taste, hardness, drug content, disintegration time and dissolution profiles. Thus, the results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated dosage forms in the oral cavity.

Incompatibility of Bisoprolol Fumarate with Some Super-disintegrating Agents

Aims: Bisoprolol fumarate, a selective β1adrenoreceptor blocker, is usually formulated as immediate release tablet dosage form. While developing the immediate release tablet formula in laboratory, the assay and dissolution results were found below acceptance limit in some formulation. The formulations differed only in disintegrating agents. Therefore a chemical interaction was suspected with some of the disintegrants with the drug used in the formulas. The aims of this study were to find out the interaction with the specific excipient. Study Design: Consequently, a pilot study of binary mixture of Bisoprolol-excipients (conventionally used in solid dosage form, e.g. binder, diluents, disintegrating agents, glidants, dissolution enhancer etc.) was carried out in laboratory using different analytical methods such as dissolution tester, UV, HPLC, DSC etc. Also formulated tablets were studied. Place: Study was carried in drug testing and analytical research laboratory in Center for Advanced Research in Sciences, University of Dhaka. Results: From the study, bisoprolol fumarate was found quite incompatible with ‘sodium starch glycolate’(SSG) and ‘croscarmellose sodium’(CCS) both of which are used as disintegrating agents in conventional solid dosage forms. But other disintegrating agents such as kollidon CL (KCL) has shown no interaction towards bisoprolol fumarate. Conclusion: Thus from this study we reached a valuable conclusion that bisoprolol fumarate is quite incompatible with two disintegrating agents namely sodium starch glycolate and croscarmellose sodium. With sodium starch glycolate, the drug was found to be degraded by around 19% whereas with croscarmellose sodium degradation was estimated around 13% in freshly prepared tablets. On the other hand, kollidon CL is compatible with this drug in its solid dosage formulation.

Release kinetics of papaverine hydrochloride from tablets with different excipients.

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Importance of excipient wettability on tablet characteristics prepared by moisture activated dry granulation (MADG)

For moisture activated dry granulation (MADG), microcrystalline cellulose (MCC) or silicon dioxide is recommended for the moisture absorption stage. The aim of this study was to assess the suitability of alternative excipients as moisture absorbents with regard to the disintegration mechanism of resulting lactose based placebo formulations. Beside high and low moisture MCC grades, the additions of magnesium aluminometasilicate (MAMS), pregelatinized starch (S1500), crospovidone (Kollidon CL) and carmellose calcium (ECG 505) were evaluated. High shear granulation (HSG) was conducted as a reference process. The overall disintegration time of all tablets produced by MADG was significantly faster whereas hardness yield and mass-variability were equal or superior compared to the HSG process. Powder wettability of the different moisture absorbents was identified to be a key driver for rapid disintegration, whereas tablet porosity had only a minor influence on the target hardness of the tablets.

Compressibility and dissolution characteristics of mixed fruit tablets made from guava and pitaya fruit powders

This study reports the tableting of whole fruit powder from pitaya and guava and their dissolution in relation to use as drink's tablets. Pulps of both fruits with peels and seeds were freeze-dried into powders with addition of 10% maltodextrin. The fruit powders, individually as well as in a binary mixture (1:1), were analyzed for material properties and were found to be poor in flow. Among the three powders, guava powder attained the lowest density during compaction and exhibited as a poor compressible powder. Mixed fruit tablets containing 1% effervescent agent eroded quite fast in all three types of solvents studied. However, the acidic solvent (0.1 N HCl) was found to be not suitable for erosion of tablets containing polyvinypolypyrrolidone (Kollidon CL). In terms of active ingredient release (antioxidant), Kollindon CL was found to be the best. In the case of color release (a⁎), the faster the erosion, the better was the color intensity irrespective of dissolution media. As drink tablets, the mixture containing 10% sugar was highly preferred by majority of panelists (80%). A month long storage study with the mixed fruit tablet formulation at room temperature showed good microbial stability.

Fexofenadine HCl Immediate Release Tablets: In vitro Characterization and Evaluation of Excipients

Fexofenadine HCl immediate release tablets were designed to increase the dissolution rate by using superdisintegrants. Different formulations of Fexofenadine HCl were prepared by direct compression method. These formulations were evaluated for hardness, thickness, friability, weight variation, disintegration time, and in vitro dissolution study. The drug release from the formulations were studied according to USP specification (USP paddle method at 50 rpm for 60 minutes) maintaining the temperature to 37°C. Sodium starch glycolate, cross carmellose sodium, crospovidone (kollidon CL), ludiflash and xanthan gum were used in 3%, 6% and 8% concentrations as superdisintegrants. Thus, the ratio of superdisintegrants was changed whereas all the other excipients as well as the active drug (Fexofenadine HCl) remained same in every formulation. Here, 0.001N HCl was used as dissolution medium according to USP and absorbances were determined by using UV spectrophotometer at 217 nm. The F-3 and F-6 formulation prepared by 8% of Sodium starch glycolate and 8% of Cross carmellose sodium showed 99.99% drug release within 30 minutes and 45 minutes, respectively. The disintegration times of F-3 and F-6 formulation were within 9 seconds. The interactions between drug and excipients were characterized by FTIR spectroscopic study. DOI: http://dx.doi.org/10.3329/bpj.v16i1.14483 Bangladesh Pharmaceutical Journal 16(1): 1-9, 2013

An easy-to-use approach for determining the disintegration ability of disintegrants by analysis of available surface area

With the aim of directly predicting the functionality and mechanism of disintegrants during the disintegration and dissolution of tablets, we investigated an analysis method based on available surface area, which is the surface area of a drug in a formulation in direct contact with the external solvent during dissolution. We evaluated the following disintegrants in this study: sodium starch glycolate (Glycolys), crospovidone (Kollidon CL), carboxymethylcellulose calcium (CMC-Ca), low-substituted hydroxypropylcellulose (L-HPC), and croscarmellose sodium (Ac-Di-Sol). When disintegrant was added to a 50% ethenzamide tablet formulation, an increase in the dissolution rate dependent on disintegrant concentration was observed, according to the type of disintegrant. In addition, the available surface area also differed between disintegrants. For Glycolys, CMC-Ca, and Ac-Di-Sol, a rapid increase in available surface area and a large increase in maximum available surface area (Smax) were observed due to high swellability and wicking, even when the disintegrant concentration was only 1.0%. In contrast, for Kollidon CL and LH-21, a gradual increase in available surface area was observed, depending on the disintegrant concentration. To evaluate the disintegrant ability, Δtmax and ΔSmax were calculated by subtracting peak time (tmax) at 5.0% from that at 1.0% and subtracting Smax at 1.0% from that at 5.0%, respectively, and it was found that the water absorption ratio had strong negative correlations with Δtmax and ΔSmax. Therefore, this study demonstrates that analysis of only available surface area and parameters thereby obtained can directly provide useful information, especially about the disintegration ability of disintegrants.

OPTIMIZATION OF GRANULE SIZE AND DISINTEGRANTS ON FORMULATION OF RAPID DISPERSIBLE TABLETS OF TOLFENAMIC ACID

Optimization of formulation is the backbone of any robust formulation. Tolfenamic Acid is an orally and parenterally administered Non – steroidal anti-inflammatory drug belonging to the fenamate group. As per the British pharmacopoeia, uniformity of dispersion and fineness of dispersion is the basic requirement of Orodispersible tablets. Delay in dispersion times, variation in dispersion, poor wetting tendency of formulation is some of the measurable factors showing insufficient optimization in formulation of rapid dispersible tablets. The size of granules plays a major role in disintegration and dispersion of rapid dispersible tablets. The present study was aimed to optimize the size of granules and selection of efficient disintegrants for rapid dispersible tablets of Tolfenamic acid. The present work studies effect of various size fractions of granules with superdisintegrants as Explotab, Ac di sol, Kyron T-314, Kollidon CL to determine the influence of disintegrant type and optimization of dispersion. Tolfenamic acid was co-micronized with microcrystalline cellulose and surfactants as sodium Lauryl sulfate. The formulation was than evaluated for various physical and analytical properties of rapid dispersible tablets. Results obtained showed that there was a significant increase in dissolution rate of drug with ac di sol and in first 5 minutes of time interval. The size of granules fraction also having a clear impact on dispersion and fineness of dispersion, the dispersion time was increasing with increasing the granules size fractions. Â

Polymeric coatings for a multiple-unit pulsatile delivery system: Preliminary study on free and applied films

In order to adapt a previously described swellable/erodible pulsatile delivery system to a multiple-unit configuration, insoluble films with adequate permeability and flexibility were proposed for application to its functional hydroxypropyl methylcellulose (HPMC) layer. By slowing down the penetration of water into the system, such films would be expected to improve the relevant effectiveness in delaying the onset of release without possibly impacting on the mechanism involved. Free films of Eudragit(®)NE containing differing amounts (10-20%) of a superdisintegrant, i.e. Explotab(®)V17, Ac-Di-Sol(®), Kollidon(®)CL or Kollidon(®)CL-M, were prepared by spraying technique and evaluated for hydration, permeability and tensile properties. The hydration and permeability characteristics were enhanced by the addition of the superdisintegrants, generally as a function of their concentration. Explotab(®)V17 was shown particularly useful to increase the film permeability. Moreover, it exerted a minor impact on the advantageous tensile properties of the acrylic polymer, especially in the wet state. Based on these results and on a preliminary release study performed with two-layer devices, the Eudragit(®)NE film with Explotab(®)V17 at the highest investigated percentage was identified as a potential formulation candidate for being applied to HPMC-coated cores thus allowing the onset of release to effectively be delayed by coatings of reduced thickness.

Rapidly Disintegrating Tablets Containing Taste Masked Clarithromycin

The objective of this study was to mask the bitter taste of clarithromycin and to formulate rapidly disintegrating tablets (RDT) of the taste masked drug. Taste masking was achieved by melt granulation method using cetyl alcohol as meltable binder. Dissolution aid (KollidonCL) was added in the formulation to improve the dissolution rate of taste masked granules as the lipids are known to retard the dissolution. The formulation having drug-lipid-dissolution aid ratio of 1:1:0.15 showed significant taste masking, confirmed by drug release study in phosphate buffer pH 6.8 and taste evaluation. Taste evaluation of taste masked granules in human volunteers revealed considerable taste masking within 10s, whereas claritromycin was rated as very bitter with a score of +4 for 10s. The taste masked granules were formulated as rapid disintegrating tablets using disintegrant addition approach. Tablets were evaluated for various parameters such as hardness, friability, drug content, in-vitro and in-vivo disintegration time and dissolution rate. Tablets of batch F6 containing Kollidon CL as superdisintegrating agent showed faster disintegration. Dissolution profile of optimized RDT in phosphate buffer pH 6.8 showed reduction in dissolution rate initially but more than 85% drug was dissolved after 45 min. The release profile thus obtained proved that the tablet could provide effective taste masking characteristics without compromising with dissolution rate.

Development and Characterization of Enteric-Coated Immediate-Release Pellets of Aceclofenac by Extrusion/Spheronization Technique Using κ-Carrageenan as a Pelletizing Agent

In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion-spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like beta-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% kappa-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of kappa-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.