Formulation Development and Process Scale Up of a High Shear Wet Granulation Formulation Containing a Poorly Wettable Drug

He, Xiaorong; Lunday, Keith A.; Li, Liang‐chi; Sacchetti, Mark

doi:10.1002/jps.21410

Cited by 15 publications

(5 citation statements)

References 15 publications

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“…However, applied shear does not always slow down drug dissolution. Although high-shear granulation can be used to decrease the drug dissolution consistently 11 , use of low shear force can also increase the dissolution time 12 . In other words, depending on composition, both high shear and low shear can increase the dissolution time for different conditions.…”

Section: Introductionmentioning

confidence: 99%

“…In other words, depending on composition, both high shear and low shear can increase the dissolution time for different conditions. In addition to process shear conditions (i.e., shear rate), lubrication time (i.e., strain) also significantly affects the drug dissolution 12 . In addition, high-shear blenders can result in uncontrolled particle size reduction if the applied shear is high.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

Pingali

Méndez

Lewis

et al. 2010

Drug Development and Industrial Pharmacy

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Objective-The purpose of this study was to investigate the effect of mechanical shear on hydrophobicity of pharmaceutical powder blends as a function of composition and particle size, and to determine the impact on drug release from tablets.Methods-Four powder formulations were subjected to three different shear strain conditions (40 rev, 160 rev, and 640 rev) in a controlled shear environment operating at a shear rate of 80 rpm. A total of 12 blends were tested for hydrophobicity. Subsequently, sheared blends were compressed into tablets at 8 kN and 12 kN in a rotary tablet press. During tablet compression, powder samples were collected after the feed frame and their hydrophobicity was again measured.Results-Results indicated that increase in shear strain could significantly increase hydrophobicity, predominantly as an interacting function of blend composition. Blends with both colloidal silica and magnesium stearate (MgSt) were found to show higher hydrophobicity with shear than other blends. Additional shear applied by the tablet press feed frame was found to change the powder hydrophobicity only in the absence of MgSt.Conclusions-Studies showed that the drug release rates dropped with shear more for the blends with both colloidal silica and MgSt than the other blends. Furthermore, the rate of drug release dropped with a decrease in particle size of the main excipient. Surprisingly, the relationship between the relative increase in hydrophobicity and a corresponding drop in the drug release rate was not found when either MgSt or colloidal silica was mixed alone in the blends.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

Pingali

Méndez

Lewis

et al. 2010

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

show abstract

“…The hot-melt granulation was carried out in 25 L jacketed Rapid Mixer Granulator involving granulation in 3 lots, cooling in 3 lots, sifting, milling followed by blending and lubrication in 1 lot [27, 28]. The lubricated blend, after release was compressed to 130,000 tablets.…”

Section: Methodsmentioning

confidence: 99%

“…System suitability was considered to have relative standard deviation for six replicate standard injections not more than 15.0% against each solvent. The residual solvent content in the dosage forms (in ppm) was calculated using the equation 5 [27] as (AT/AS)×(WS/100)×(10/100)×(5/WT)×( P /100) × 10 6 , where AT = peak area of corresponding solvent in sample injection; AS = peak area of corresponding solvent in standard injection; WS = weight of corresponding solvent standard taken in mg; WT = weight of sample taken in mg; P = percentage purity of corresponding solvent standard.…”

Section: Methodsmentioning

confidence: 99%

In Vitro-In Vivo Correlation Evaluation of Generic Alfuzosin Modified Release Tablets

Sanki

Mandal

2012

ISRN Toxicology

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Alfuzosin, a selective alpha-1a antagonistis is the most recently approved AARAS, with limited cardiac toxicity and exclusively used for lower urinary tract syndromes (LUTS). In order to reduce pill burden and better patient compliance modified release (MR) formulations have been developed. Alfuzosin MR tablet was developed by the use of hot-melt granulation techniques using mono- and diglycerides as rate controlling membranes to minimize health care cost and uses of costly excipients. The other purpose of the study was to evaluate in vitro-in vivo performance of the scale up batch in healthy human subjects for commercialization. The blend uniformity (mean ± RSD%), assay, cumulative percent dissolution at 24 h, hardness, and friability of the biobatch were 100.2 ± 0.05%, 100.43 ± 0.023%, 93.98%, 4.5 kg, 5 min, and 0.08%, respectively. The in vivo pharmacokinetic parameters under fasting conditions between test and reference formulations (Uroxatral 10 mg extended release tablets) were comparable. The 90% CI, geometric mean ratio (%) and power of C max, AUCT, and AUCI of the fasting study for the test and reference formulation were 99.03% to 122.78%, 109%, 0.998; 92.94% to 116.71%, 104%, 1; 98.17% to 124.01%, 110% 1, respectively. The scale up biobatch showed negligible difference in in vitro properties with respect to the pilot batch. The formulation developed with these agents was safe to use as there were no serious adverse events developed during the conduction of the clinical trial on the healthy subjects. Furthermore, the developed formulation was bioequivalent with respect to rate and extends of absorption to the reference formulation.

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“…Pharmaceutics: The practical development of pharmaceutics encompasses the preparation of new recipes containing more efficient active principles, followed by the scale-up of the preparation technologies developed in the lab, such as wet granulation or hot melt mixing. Faure et al (2001) reviewed the techniques used for process control and scale-up of wet granulation processes, while He et al (2008) applied a strategy based on statistical analysis of experiments for shear wet granulation. In the case of lyophilization, Kramer et al (2009) combined empirical testing and numerical modeling to scale-up commercial equipments.…”

Section: Scale-up In Science and Engineeringmentioning

confidence: 99%

An Engineering Scale-Up Approach using Multi-Objective Optimization

Gaspar‐Cunha

Covas

2014

International Journal of Natural Computing Research

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In science and engineering, researchers are often challenged with the need to replicate the innovative results obtained with an equipment of a given size in another equipment of a different dimension. In practice, this often involves passing from laboratory or prototype dimensions to industrial level. The process is known as scale-up and consists in ensuring that the values of the criteria that describe the process characteristics at a given scale are preserved at different scales. Typically, this might involve a chemical reaction rate and/or conversion, a total residence time, specific flow and/or heat transfer characteristics, a certain degree of mixing, etc. Available scale-up rules are often based on oversimplified process analyses and generate unsatisfactory results. Scale-up can also be understood as an optimization process where various objectives are to be satisfied simultaneously, i.e., the performance at the two scales must be as similar as possible. For that purpose, the adoption of a multi-objective optimization algorithm is proposed. The technique is illustrated with an example from polymer engineering.

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Formulation Development and Process Scale Up of a High Shear Wet Granulation Formulation Containing a Poorly Wettable Drug

Cited by 15 publications

References 15 publications

Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

In Vitro-In Vivo Correlation Evaluation of Generic Alfuzosin Modified Release Tablets

An Engineering Scale-Up Approach using Multi-Objective Optimization

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