Package Selection for Moisture Protection for Solid, Oral Drug Products

Waterman, Kenneth C.; MacDonald, Bruce C.

doi:10.1002/jps.22161

Cited by 101 publications

(85 citation statements)

References 47 publications

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“…When compared within the same storage time, however, samples taken from closer to the surface showed greater absorption. In their study of the effect of pH on the generation of magnesium carbonate hydrates (magnesite [ Zhang et al reported that the main product was hydromagnesite at higher pH conditions; this has a planar structure and its examination by FT-IR showed that the CO 3 2− absorption was around 1400-1500 cm −1 , while the OH and crystal water absorption was around 3400-3600 cm −1 . 13) These results suggested that the tablet mass changes during storage involved water absorption by MgO and also absorption of CO 2 gas, and that hydromagnesite was produced more predominantly at the tablet surface, from the early stages of storage.…”

Section: Resultsmentioning

confidence: 99%

“…Volume was calculated by dividing this mass by the true density of hydromagnesite (2.2 g/ mL 11,12) ). [4] The mass of the residual unreacted MgO after storage was calculated by subtracting [3] from the mean mass of the tablet (mg) after storage. The true density of MgO was measured using a dry automatic pycnometer (AccuPyc 1330, Shimadzu Corporation, Kyoto, Japan) and the volume was calculated by dividing this mass by the determined density (3.17 g/mL).…”

Section: Calculation Of Tablet Porositymentioning

confidence: 99%

“…The true density of MgO was measured using a dry automatic pycnometer (AccuPyc 1330, Shimadzu Corporation, Kyoto, Japan) and the volume was calculated by dividing this mass by the determined density (3.17 g/mL). [5] The tablet void volume (mL) was calculated by subtracting the sum of the volumes determined in [3] and [4] from the tablet volume (mL), which was calculated using the mean size and thickness after storage. The porosity was this void volume, expressed as a percentage of the tablet volume.…”

Section: Calculation Of Tablet Porositymentioning

confidence: 99%

“…However, uncoated tablets are affected by the temperature, humidity, and light-exposure of their storage environment; humidity in particular often affects the physical properties of tablets by reducing hardness and changing (accelerating or delaying) their disintegration time. [1][2][3][4] For this reason, uncoated tablets are usually packaged using materials with a high moisture resistance, such as pillowtype packaging with aluminum foil. In recent years, however, uncoated tablets have also often been handled in an unpackaged state, such as in automatic tablet packing machines, to provide unit-dose packages that aim to improve the reliability of, and compliance to, drug therapies.…”

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confidence: 99%

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Mechanism by Which Magnesium Oxide Suppresses Tablet Hardness Reduction during Storage

Sakamoto

Kachi

Nakamura

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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This study investigated how the inclusion of magnesium oxide (MgO) maintained tablet hardness during storage in an unpackaged state. Tablets were prepared with a range of MgO levels and stored at 40°C with 75% relative humidity for up to 14 d. The hardness of tablets prepared without MgO decreased over time. The amount of added MgO was positively associated with tablet hardness and mass from an early stage during storage. Investigation of the water sorption properties of the tablet components showed that carmellose water sorption correlated positively with the relative humidity, while MgO absorbed and retained moisture, even when the relative humidity was reduced. In tablets prepared using only MgO, a petal-or platelike material was observed during storage. Fourier transform infrared spectrophotometry showed that this material was hydromagnesite, produced when MgO reacts with water and CO 2 . The estimated level of hydromagnesite at each time-point showed a significant negative correlation with tablet porosity. These results suggested that MgO suppressed storage-associated softening by absorbing moisture from the environment. The conversion of MgO to hydromagnesite results in solid bridge formation between the powder particles comprising the tablets, suppressing the storage-related increase in volume and increasing tablet hardness.Key words hydromagnesite; relative humidity; unpackaged state; capillary condensation; mesopore Tablets are frequently used as a drug dosage form that is convenient for patients. However, uncoated tablets are affected by the temperature, humidity, and light-exposure of their storage environment; humidity in particular often affects the physical properties of tablets by reducing hardness and changing (accelerating or delaying) their disintegration time. [1][2][3][4] For this reason, uncoated tablets are usually packaged using materials with a high moisture resistance, such as pillowtype packaging with aluminum foil. In recent years, however, uncoated tablets have also often been handled in an unpackaged state, such as in automatic tablet packing machines, to provide unit-dose packages that aim to improve the reliability of, and compliance to, drug therapies. The packaging materials used for unit-dose packaging are not generally completely moisture-resistant, and the tablets in these packages reportedly show decreased hardness. 4,5) Magnesium oxide (MgO) has frequently been used as a laxative and antacid and has been proven to be effective and safe. MgO tablets have also become widespread in recent years because they are easy to take. [6][7][8] When stored for three months in an unpackaged state at 30°C with 75% relative humidity, these MgO tablets (Magmitt Tab ® , and Maglax Tab ® ) showed a 1.7-3.8-fold increase in hardness.9) MgO accounts for 86-88% of the mass of these tablets, strongly implying that MgO is involved in this increase in hardness. We have previously shown that MgO is useful as an excipient that suppresses the decline in tablet hardness caused by humidity.10)The...

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Section: Resultsmentioning

confidence: 99%

Section: Calculation Of Tablet Porositymentioning

confidence: 99%

Section: Calculation Of Tablet Porositymentioning

confidence: 99%

mentioning

confidence: 99%

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Mechanism by Which Magnesium Oxide Suppresses Tablet Hardness Reduction during Storage

Sakamoto

Kachi

Nakamura

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The main functions targeted for various products are small oxygen permeability or oxygen scavenging [5][6][7], humidity control [8][9][10][11][12], regulated ethylene content [13], antimicrobial effect [14][15][16][17], adsorption of odorous materials, or the opposite, the release of desirable aromas [18,19]. Intensive research and development work is carried out on these materials all over the world, but mostly in industry.…”

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Decreased oxygen permeability of EVOH through molecular interactions

Péter¹,

Kenyó²,

Renner³

et al. 2014

Express Polym. Lett.

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The number of functional and smart packaging materials increases continuously and they are used already in everyday practice in increasing quantities [1][2][3][4]. The main functions targeted for various products are small oxygen permeability or oxygen scavenging [5][6][7], humidity control [8][9][10][11][12], regulated ethylene content [13], antimicrobial effect [14][15][16][17], adsorption of odorous materials, or the opposite, the release of desirable aromas [18,19]. Intensive research and development work is carried out on these materials all over the world, but mostly in industry.Controlling oxygen permeability is especially important in the pharmaceutical industry and in food packaging. The oxygen permeability of polymers varies in a wide range covering several orders of magnitudes from a few hundred to a few hundredths or even thousands of cm 3· mm/m 2 /24 h/bar [20]. Ethylene-vinyl alcohol copolymers (EVOH) offer extremely good protection against oxygen [20][21][22][23][24][25]. The barrier properties of these materials depend on ethylene content [23,26,27], crystallinity, temperature [22,28] and humidity [24,[26][27][28][29][30][31][32][33][34]. The last factor represents also the major drawback of EVOH, since permeability may increase by orders of magnitudes with increasing water content [28] Abstract. Poly(ethylene-co-vinyl alcohol) of 48 mol% ethylene content was modified with N,N!-bis(2,2,6,6-tetramethyl-4-piperidyl)-isophthalamide (Nylostab SEED) to decrease the oxygen permeability of the polymer. The additive was added in a wide concentration range from 0 to 10 wt%. The structure and properties of the polymer were characterized with various methods including differential scanning calorimetry, X-ray diffraction, mechanical testing, optical measurements and oxygen permeation. Interactions were estimated by molecular modeling and infrared spectroscopy. The results showed that oxygen permeation decreased considerably when the additive was added at less than 2.0 wt% concentration. The decrease resulted from the interaction of the hydroxyl groups of the polymer and the amide groups of the additive. The dissolution of the additive in the polymer led to decreased crystallinity, but also to decreased mobility of amorphous molecules. Stiffness and strength, but also deformability increased as a result. Above 2 wt% the additive forms a separate phase leading to the deterioration of properties. The success of the approach represents a novel way to control oxygen permeation in EVOH and in other polymers with similar functional groups capable of strong interactions.

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Overview of Drug Product Development

Narayan

2011

CP Pharmacology

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The process for developing drug delivery systems has evolved over the past two decades with more scientific rigor, involving a collaboration of various fields, i.e., biology, chemistry, engineering, and pharmaceutics. Drug products, also commonly known in the pharmaceutical industry as formulations or "dosage forms," are used for administering the active pharmaceutical ingredient (API) for purposes of assessing safety in preclinical models, early- to late-phase human clinical trials, and for routine clinical/commercial use. This overview discusses approaches for creating small-molecule API dosage forms, from preformulation to commercial manufacturing.

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Package Selection for Moisture Protection for Solid, Oral Drug Products

Cited by 101 publications

References 47 publications

Mechanism by Which Magnesium Oxide Suppresses Tablet Hardness Reduction during Storage

Mechanism by Which Magnesium Oxide Suppresses Tablet Hardness Reduction during Storage

Decreased oxygen permeability of EVOH through molecular interactions

Overview of Drug Product Development

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