Changes In Dissolution Profiles Research Articles

FORMULATION AND EVALUATION OF FILM COATED TABLETS CONTAINING ACECLOFENAC AND PARACETAMOL

FORMULATION AND EVALUATION OF FILM COATED TABLETS CONTAINING ACECLOFENAC AND PARACETAMOL

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.

Triacetylated andrographolide solid dispersions: Preparation, stability study and in vivo anti-inflammation in mice ulcerative colitis model

This manuscript reported a preliminary study of triacetylated andrographolide solid dispersion (TA-SD) that investigated the influence of preparation method and carrier materials on the physical stability of prepared SDs, and tested the anti-inflammatory effect of TA-SD. SDs were prepared by hot-melt extrusion (HME) or solvent-evaporation (SE) with fixed drug loading of 10% using Kollidon VA64 (VA64-SD) or Soluplus (So-SD) as carriers. The physical stability of the four prepared SDs was studied after a 7-day exposure to heat (30 °C and 60 °C) or moisture (75% and 92.5% relative humidity). All SDs samples, except So-SD prepared by HME (So-HME-SD), were found with drug recrystallization after 7-day exposure to 92.5% RH, as illustrated by DSC analysis. All prepared SDs showed reduced dissolution after storage under stressed conditions, and according to their changes in dissolution profiles, it was found that So-SDs were more sensitive to heat while VA64-SDs were more sensitive to moisture, and SDs prepared by HME could inhibited drug recrystallization more effectively. In anti-inflammatory study, TA solid dispersion prepared by HME using VA64 as carrier material showed comparable therapeutic effect against ulcerative colitis with commercial andrographolide drop pills but significant improved activity over crude TA suspension, indicating the necessity of solid dispersion preparation.

Effects of Storage Conditions on Dissolution Rates of Indomethacin Capsules.

Using indomethacin (IND) capsules (Caps) before the date of expiration, we conducted the dissolution tests that are prescribed in the 17th Revision Japanese Pharmacopoeia (JP 17) and found a preparation within a serial number (Lot) that failed to satisfy the specified dissolution rate. Thus, we investigated factors that decrease dissolution rates of IND Caps during storage at room temperature (r.t.). In elution profiles of IND Caps samples, dissolution rates decreased as the expiration date approached. Moreover, after extended elution of formulations with unacceptable 20 min dissolution rates, dissolution rates remained in less of those specified in JP 17. Moreover, changes in dissolution profiles of preparations with pending expiry did not reflect changes in Caps shells, suggesting changes in the active contents. However, IND contents of the offending preparations decreased very little, even under accelerated conditions. Thus, in further experiments, we investigated preservation conditions of IND Caps, and found that humidity greatly decreases dissolution rates, and preservation of press-through package (PTP) sheets were also suggested to affect IND Caps. Finally, we found that the use of aluminum bag packaging prevents decreases in dissolution rates of IND Caps.

Preparation, characterization and in vivo evaluation of curcumin self-nano phospholipid dispersion as an approach to enhance oral bioavailability

The aim of this study was to examine the efficacy of self-nano phospholipid dispersions (SNPDs) based on Phosal® to improve the oral bioavailability of curcumin (CUR). SNPDs were prepared with Phosal® 53 and Miglyol 812 at different surfactant ratio. Formulations were evaluated for particle size, polydispersity index, zeta potential, and robustness toward dilution, TEM as well as in vitro drug release. The in vivo oral absorption of selected formulations in comparison to drug suspension was evaluated in rats. Moreover, formulations were assessed for in vitro characteristic changes before and after storage.The SNPDs were miscible with water in any ratio and did not show any phase separation or drug precipitation. All the formulas were monodisperse with nano range size from 158±2.6nm to 610±6.24nm. They passed the pharmacopeial tolerance for CUR dissolution. No change in dissolution profile and physicochemical characteristics was detected after storage. CUR–SNPDs are found to be more bioavailable compared with suspension during an in vivo study in rats and in vitro release studies failed to imitate the in vivo conditions. These formulations might be new alternative carriers that enhance the oral bioavailability of poorly water-soluble molecules, such as CUR.

Design and Evaluation of a Novel Gas Formation-Based Multiple-Unit Gastro-Retentive Floating Drug Delivery System for Quetiapine Fumarate

Purpose: To develop a gastro-retentive formulation of quetiapine fumarate in the form of floating minitablets.Methods: The system consisted of core units prepared by direct compression process, which were coated with three successive layers, namely, an inner seal coat, effervescent layer and an outer polymeric layer of polymethacrylates.Results: Mini-tablets coated with Eudragit RS 30D (5, 7.5 and 10%) released . 85% of the drug after 12 h, while those coated with Eudragit RL 30D (5, 7.5 and 10%) released . 85% drug within the same period. Drug release kinetic studies showed that drug diffusion fitted best to zero order and Higuchi models, indicating that drug release was anomalous non-Fickian transport. In vivo gastric residence time results indicate that the units remained in the stomach for about 6 h (n = 3). There was nosignificant change in dissolution profiles before and after storage at 40‹C and 75% RH for 6 months.Conclusion: The developed floating mini-tablets of quetiapine fumarate exhibit prolonged release for .12 h, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations. Keywords: Mini-tablets; Floating delivery system; Effervescence, Polymeric membrane, Controlled release, Quetiapine fumarate

Stability and Comparative Dissolution Studies of Five Brands of Norfloxacin Tablets Marketed in Addis Ababa, Ethiopia

The dissolution profiles of five different brands of norfloxacin (400 mg) tablets designated as A, B, C, D, and E, marketed in Addis Ababa were compared with those of an innovator product (F). The stability of these tablets was evaluated under the influence of accelerated conditions (40 °C + 2 °C and 75% ± 5% RH). The t50% and t90% (time required for releasing 50% and 90% of the drug, respectively) were used as dissolution parameters to compare the dissolution profiles of the tablets. The t50% results indicated that except for Product C, all the others released 50% of the drug below 10.2 min (the time taken by the innovator product to release 50%). However, the t90%s for three products (B, C, and E) were longer (42.1, 37.4 and 29.0 min, respectively) than that of the innovator product (17.6 min) showing slower dissolution rates for the brand products relative to the innovator product. Product D showed a faster dissolution rate than the innovator product with 90% release at 9.8 min. The stability testing revealed that during the six months storage under the accelerated conditions, physical changes like film cracking, decrease in hardness, increase in moisture content and changes in dissolution profiles have occurred. The highest change in drug content was 3.6% at six-months. Accordingly, no significant change in drug content has occurred in any of the investigated norfloxacin tablets stored under stressed conditions for six months.Keywords: norfloxacin, film coated tablet, dissolution profile, stability, accelerated conditions

Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy

Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials® to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.

Formulation and evaluation of multiple tablets as a biphasic gastroretentive floating drug delivery system for fenoverine

A biphasic gastroretentive drug delivery system of fenoverine was developed to maintain constant plasma concentration. The delivery system consisted of a loading-dose tablet and a floating multiple matrix tablet prepared by the direct compression process. The drug release from biphasic GRDDS in 0.1 mol L(-1) HCl and SGF (enzyme free) was sustained over 12 h with buoyant properties. Stability studies showed no significant change in dissolution profiles (f2 value > 50). Based on the release kinetics, it can be concluded that the floating multiple matrix tablet containing HPMC was a particularly suitable gastroretentive drug delivery system with a zero-order release profile.

Influence of Splitting on Dissolution Properties of Metoprolol Tablets

The objective of this work was to compare several profiles of dissolution data for metoprolol controlled release tablet formulations in order to identify possible changes in dissolution profiles of whole and scored tablets. Adequate design of score lines (on one or both sides) as well as the technology of preparation of tablet mixtures ensure forming a score line of adequate thickness, shape, size, curvature. According to the obtained results, this type of extended release formulation is eligible for splitting and use in therapy either as a whole or scored tablets.

Design and evaluation of polymeric coated minitablets as multiple unit gastroretentive floating drug delivery systems for furosemide

A gastro retentive floating drug delivery system with multiple-unit minitablets based on gas formation technique was developed for furosemide. The system consists of core units (solid dispersion of furosemide:povidone and other excipients), prepared by direct compression process, which are coated with two successive layers, one of which is an effervescent (sodium bicarbonate) layer and other one an outer polymeric layer of polymethacrylates. The formulations were evaluated for pharmacopoeial quality control tests and all the physical parameters evaluated were within the acceptable limits. Only the system using Eudragit RL30D and combination of them as polymeric layer could float within acceptable time. The time to float decreased as amount of the effervescent agent increased and, when the coating level of polymeric layer decreased. The drug release was controlled and linear with the square root of time. By increasing coating level of polymeric layer decreased the drug release. The rapid floating and the controlled release properties were achieved in this present study. The stability samples showed no significant change in dissolution profiles (f(2) = 81). The in vivo gastric residence time was examined by radiograms and it was observed that the units remained in the stomach for about 6 h.

Design and Evaluation of a Novel Matrix Type Multiple Units as Biphasic Gastroretentive Drug Delivery Systems

A biphasic gastroretentive floating drug delivery system with multiple-unit mini-tablets based on gas formation technique was developed to maintain constant plasma level of a drug concentration within the therapeutic window. The system consists of loading dose as uncoated core units, and prolonged-release core units are prepared by direct compression process; the latter were coated with three successive layers, one of which is seal coat, an effervescent (sodium bicarbonate) layer, and an outer polymeric layer of polymethacrylates. The formulations were evaluated for quality control tests, and all the parameters evaluated were within the acceptable limits. The system using Eudragit RL30D and combination of them as polymeric layer could float within acceptable time. The drug release was linear with the square root of time. The rapid floating and the controlled release properties were achieved in this present study. When compared with the theoretical release profile, the similarity factor of formulation with coating of RS:RL (1:3)-7.5%, was observed to be 74, which is well fitted into zero-order kinetics confirming that the release from formulation is close to desired release profile. The stability samples showed no significant change in dissolution profiles (p > 0.05). In vivo gastric residence time was examined by radiograms, and it was observed that the units remained in the stomach for about 5 h.

Strong cation exchange resin for improving physicochemical properties and sustaining release of ranitidine hydrochloride

In the present study strong cation exchange resin (Amberlite IRP69) was used to improve the physicochemical properties of ranitidine hydrochloride such as taste and bulk properties and to sustain dissolution rate. Drug-resin complexes were prepared using batch method. Drug loading was done under different processing conditions such as temperature, pH, drug-resin ratio, and drug concentration to get the optimum condition for resinate preparation. Resinate prepared under optimized condition was tested for taste, bulk properties and release rate. Degree of bitterness of ranitidine was found to reduce to zero after complexation with resin. Improvement in flow properties was also observed. Angle of repose for resinate was found to be 33.21 o as compared to 42.27 o for ranitidine HCl. Effect of dissolution medium and particle size on in vitro release of drug from resinate was also investigated. Resinate with drug to resin ratio of 2:3 and particle size >90 µm showed about 90% of drug release within 12 h. The orodispersible tablet formulated from the resinate containing 10% croscarmellose sodium disintegrated within 35 sec in oral cavity and showed similar dissolution profile as the resinate. Tablets were found stable after stability studies with no change in dissolution profile.

Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. IV. Study on reduced-pressure mixing for practical use of amorphous mixtures of flufenamic acid.

Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) at a reduced pressure of about 10 to 50 mmHg employing a commercial mixer for pharmaceutical production. An amorphous state of FFA in the mixture was efficiently achieved with this equipment, and the dissolution of FFA was enhanced in comparison with that of the physical mixture. Effects of the conditions of mixing, such as pressure, temperature and rotating speed, on dissolution of FFA were determined. Through stability tests at 40 degrees C under both dry and humid conditions, no change in dissolution profiles was recognized in a 5% FFA mixture stored under any conditions. On the other hand, decreases in dissolution behavior were observed in 10% and 20% FFA mixtures when they were stored under humid conditions. These results suggested that humidity should be avoided during the storage of amorphous mixtures of FFA with MAS for production purposes.

Eudragit RL and RS Pseudolatices: Properties and Performance in Pharmaceutical Coating as a Controlled Release Membrane for Theophylline Pellets

Theophylline Active pellets were coated with Eudragit RL and RS pseudolatices in a fluidized bed. The effects of polymer ratio, additional oven drying, addition of dispersed solids, and addition of water miscible organic solvents on sustained drug release through the lates film were determined by using a modified U.S.P. Paddle dissolution method.The release rate of theophylline can be varied by changing the polymer ratio. permeability to the drug increases with an increase in the content of Eudragit RL. Additional oven drying at 60°C for 10 hours caused no significant change in the dissolution profiles. The addition of dispersed solids such as talcum and silica resulted in an increase in drug release rate. There is no significant change in dissolution profiles when 50% methanol or acetone was added to the Eudragit RS pseudolatex.

Evaluation of Soy Polysaccharide as a Disintegrating: Agent Part II: Wet Granulation

Soy polysaccharide was evaluated as a disintegrating agent in tablets made by wet granulation utilizing both lactose and dicalcium phosphate dihydrate as fillers, gelatin as a granulating agent and hydrochlorothiazide as a model drug. It was found to be more effective than starch but less effective than cross-linked carboxymethylcellulose (Ac-Di-SolR) at equivalent concentrations. Soy polysaccharide appears to reduce the friability of tablets as concentration increases. Tablets containing either Soy polysaccharide or cross-linked carboxymethylcellulose showed no changes in dissolution profiles after storage under ambient conditions for six months.