Influence of shear intensity and total shear on properties of blends and tablets of lactose and cellulose lubricated with magnesium stearate

Mehrotra, Amit; Llusa, Marcos; Faqih, Abdul Mobeen N.; Levin, Michael; Muzzio, Fernando J.

doi:10.1016/j.ijpharm.2006.12.013

Cited by 67 publications

(34 citation statements)

References 27 publications

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“…The small scale of the blender and the mild mixing conditions (speed and time) minimize exposure of the lubricant to shear and are not enough to cause complete homogenization of the lubricant. Therefore, as shown in a previous publication [3] for blends with a 1% and 2% MgSt content, after mixing the lubricant in the V-blender and even processing the blend in the shear cell for a low number of revolutions, lubricant homogeneity (measured by RSD) is in the range of 5-7%. For larger shear exposure, lubricant RSD values are between 1% and 2%.…”

Section: Procedures To Prepare Formulations Under Controlled Shear Consupporting

confidence: 57%

“…However, most lubricants are hydrophobic compounds and can alter blend hydrophobicity (also known as wettability). The latter blend property affects the performance of post-lubrication steps of a tablet manufacturing process, such as compaction or tablet coating, and properties of the final product such as tablet and capsule dissolution and tablet strength [3]. In addition, blend hydrophobicity affects a granulation process: high substrate hydrophobicity may lead to inadequate binder distribution which in turn means weak, porous granules.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

Llusa

Levin²,

Snee

et al. 2010

Powder Technology

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Section: Procedures To Prepare Formulations Under Controlled Shear Consupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

Llusa

Levin²,

Snee

et al. 2010

Powder Technology

Self Cite

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“…The excessive shear mixing of the lubricant reduces the mechanical strength of the direct compression tablets by producing a surplus coating of the finely divided magnesium stearate particles. 8) In this particular case, the mixing of the API and the lubricant is separated to meet the quality specifications of homogeneity and tablet hardness; API and the other excipients, except for the lubricant, are mixed to achieve homogeneity, and then the mixed powder is blended with the lubricant. Shear mixing of the glidant is also considered to be as important as the lubricant because the glidants are required to coat the entire surface of all host particles; however, the glidant has always been mixed with micronized API and enlarged direct compression vehicles in one operation.…”

mentioning

confidence: 99%

Improving Powder Flow Properties of a Direct Compression Formulation Using a Two-Step Glidant Mixing Process

Abe¹,

Yasui²,

Kuwata

et al. 2009

Chem. Pharm. Bull.

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Direct compression is a faster, simpler, and easier technique for tablet manufacturing compared to other processes such as wet and dry granulation techniques because it only requires mixing and compression. In addition to mixing and compression, wet granulation requires granulation, drying, and milling. Each additional step generates variability in the process and increases the risk of out-of-specification products. Fewer steps in the manufacturing process are advantageous for pharmaceutical industries; however, the application of direct compression has been limited due to issues of powder flowability, content uniformity and tabletability. A failure of powder flow often leads to abandon direct compression and adopt granulation process during formulation and process development trials. Flow has a direct impact on decision of whether to start out developing direct compression. Additionally, flowability and tabletability often develop into critical quality factors of high-dose tablets, while content uniformity causes the major concern in low-dose tablets. 1)Therefore, unfavorable powder flow is the fundamental and serious bottleneck to be first eliminated in the direct compression processing.Glidants are usually incorporated in direct compression formulations to improve powder flow and control tablet weight. Specifically, silica has been reported to be the most efficient glidant because of its small particle size and extremely low-density.2) Moreover, direct compression vehicles, such as spray-dried lactose and agglomerated lactose instead of fine-powder lactose, are commonly used to remedy flow properties. Several studies have reported that powder flowability can be significantly enhanced with the optimum concentration of porous or nonporous silica, 3) appropriate mixing time, 4) correct mixer type 5,6) and hydrophilic or hydrophobic silica properties.7) However, most of the studies have focused only on the relationships between the glidant and the direct compression vehicles and have excluded an active pharmaceutical ingredient (API), even though API powder properties are quite different from these excipients for direct compression. Generally, APIs are micronized to improve solubility and bioavailability, and consequently tend to be cohesive. In contrast, the direct compression vehicles are usually agglomerated and enlarged to become free flowing. Therefore, micronized API and enlarged direct compression vehicles are the most interesting and noteworthy factors to comprehensively improve the flow properties of a direct compression formulation. Shear mixing plays a critical role in blending for direct compression, particularly for low-dose drug products containing lubricants (e.g., magnesium stearate and calcium stearate). The homogeneity of the low-dose API requires sufficient mixing and results in excessive shear on magnesium stearate. The excessive shear mixing of the lubricant reduces the mechanical strength of the direct compression tablets by producing a surplus coating of the finely divided magnesium stearat...

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“…This behavior came as a surprise, since increased magnesium stearate content of powders was linked with improved flow characteristics (24)(25)(26) by reducing adhesion and capillary forces (27,28). Lubrication, however, is not only dependent on the lubricant content, but also on the blending time and mixing intensity.…”

Section: Evaluation Of Variables Affecting Powder Mixture Propertiesmentioning

confidence: 99%

Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design

Szabó

Székely-Szentmiklósi²,

Deák

et al. 2016

Acta Pharmaceutica

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Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental designTo evaluate the influence of different variables on tablet formulations containing enalapril maleate and indapamide as active substances, two separate experimental designs were employed: one for evaluating powder properties and the other for tablet characteristics. Because of the low active pharmaceutical ingredient content, it was hypothesized that both powder and tablet properties could be determined only by the characteristics of excipients. In order to test this assumption, both experimental designs were done with placebo mixtures. The optimized formulation was then evaluated both with and without APIs. Results indicated that filler and lubricant percentage, along with compression force, were the most important variables during the formulation study. The optimized formulation showed similar characteristics in both cases for all responses, except for angle of repose and friability where only minor differences were observed. The combination of the applied approaches (using placebo composition and fractional experimental design) proved to be efficient, cost effective and time saving.Keywords: design of experiments, optimization, factorial design, placebo formulation Proper management of hypertension, one of the leading causes of cardiovascular disease, is of the utmost importance. It has been established that lowering of blood pressure can effectively reduce the risk of cardiovascular events and stroke, but finding the most appropriate therapy is often difficult (1). Combinational therapies employing an angiotensin-converting enzyme inhibitor (ACEi) and indapamide (IND) offer the advantage of using two highly effective agents, increasing both clinical efficiency and patient compliance (2-4). Low dose combinations of ACEis and diuretics have shown greater reduction in blood pressure and higher success rates in managing hypertension than either of the treatments alone (4-6). The most popular ACEis present in these combinations include perin- Szabo et al.: Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design, Acta Pharm. 66 (2016) 191-206.

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Influence of shear intensity and total shear on properties of blends and tablets of lactose and cellulose lubricated with magnesium stearate

Cited by 67 publications

References 27 publications

Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

Improving Powder Flow Properties of a Direct Compression Formulation Using a Two-Step Glidant Mixing Process

Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design

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