Elsevier

Applied Surface Science

Volume 255, Issue 5, Part 2, 30 December 2008, Pages 2782-2786
Applied Surface Science

Effect of moisture content on solid-state interaction at the interface between magnesium stearate and captopril

https://doi.org/10.1016/j.apsusc.2008.08.009Get rights and content

Abstract

A grinding process was used to accelerate the solid-state interaction at the interface between magnesium stearate (MgSt) and captopril (CAP) in the presence or absence of water. The 110 °C-preheated MgSt/CAP or MgSt/CAP ground mixture showed a 5.06% (w/w) or 6.07% (w/w) water content, respectively, which was >4.29% (w/w) for the original MgSt alone. The increased water content in each ground mixture was due to the atmospheric absorption of water caused by grinding. A small infrared (IR) peak at 1562 cm−1 appeared in the IR spectrum of the 110 °C-preheated MgSt/CAP ground mixture, whereas a stronger IR peak at 1541 cm−1 with a shoulder at 1556 cm−1 was observed for the MgSt/CAP ground mixture. These IR peaks were possibly related to the solid-state interaction at the interface between MgSt and CAP via hydrogen bonding of adsorbed water. However, an excess of water added in the MgSt/CAP ground mixture could exacerbate the solid-state interaction of MgSt and CAP to form a stearic acid as evidenced by the IR peak at 1705 cm−1. This may be due to the neutralization between basic MgSt and acidic CAP. In addition, thermal Fourier transform infrared (FTIR) microspectroscopy also confirmed that the thermal-dependent dehydration process might alter the IR peak intensity of MgSt/CAP ground mixtures.

Introduction

The drug–excipient interaction plays an important role in influencing drug stability in the formulation, leading to significant changes in quality and efficacy of drug products. Several excipients have been reported to easily interact with some drugs in the solid state by their specific properties such as (I) acting as a moisture source, (II) forming a solid solution, or (III) acting as a reaction catalyst or chemical reactant [1], [2]. Moisture is the most commonly encountered problem whether by atmospheric absorption in the course of processing or storage, or by external addition such as wet granulation.

Lubricants are essential excipients for solid dosage forms, not only to improve the lubricating properties of ingredients in the manufacture of tablets and capsules, but also to prevent the ingredients from sticking to the manufacturing equipment [3], [4]. Among these lubricants, talc or metallic stearate is a commonly used lubricant, in which magnesium stearate (MgSt) is more preferred. MgSt is a soft powder used as a lubricant for the pharmaceutical industry and as a plastic stabilizer for the rubber industry (Fig. 1). MgSt has been extensively studied and significantly influences the disintegration and dissolution of tablets and capsules [5], [6]. Moreover, the effect of MgSt on the content uniformity of an active pharmaceutical ingredient (API) in pharmaceutical powder mixtures has also been examined [7]. Since MgSt consists of a metal ion and a wax-like stearate, it has been reported to be incompatible with many drugs [8], [9], [10]. Captopril (CAP) is an orally effective angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure [11], [12]. CAP is the first generated ACE inhibitor and possesses three unique functionalities: a mercapto, amide and carbonyl moiety in structure. In our previous study, we had proposed a possible solid-state interaction between MgSt and CAP via the hydrogen bonding of water [13]. The grinding process was used to accelerate this solid-state interaction at the interface. However, what role the amount of water plays to induce this solid-state interaction at the interface between MgSt and CAP is uncertain. It is interesting for us to further investigate the effect of water content on the solid-state interaction between MgSt and CAP. In the present study, the detailed solid-state interaction at the interface between MgSt and CAP under 5-min grinding process by adding different amounts of water was investigated by using differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and Fourier transform infrared (FTIR) spectroscopy. The effect of temperature on the solid-state interaction at the interface between MgSt and CAP after different treatments was also determined by thermal FTIR microspectroscopy.

Section snippets

Materials

Pharmaceutical grade captopril (CAP) was purchased from Bulk Med. Pharm., Hamburg, Germany. Magnesium stearate (MgSt, >100 mesh) was obtained from Wako Pure Chemical Industries, Ltd., Tokyo, Japan without further treatment. The KBr crystal was of analytical reagent grade and purchased from Jasco Parts Center (Jasco Co., Tokyo, Japan).

Preparation of MgSt/CAP ground mixture

Each MgSt/CAP ground mixture containing different amounts of water (weight ratio of MgSt:CAP:water = 1:1:0.2:0.8) was prepared by grinding in a ceramic mortar for 5 

Results and discussion

The grinding process was used to improve the mobility and create more surface area for accelerating the possible interaction at the interface between MgSt and CAP. According to our preliminary study, the ground sample was optimally prepared by co-grinding the physical mixture of MgSt and CAP with the same weight ratio for 5 min before analytical determination. Here, different amounts of water were added into the mixture during the grinding process. Fig. 2A shows DSC and TG curves for the

Conclusions

The present study indicates that the grinding process could significantly induce the absorption of moisture from atmosphere to accelerate the solid-state interaction at the interface between MgSt and CAP. The higher water content in the MgSt/CAP ground mixture might exacerbate the solid-state interaction of MgSt and CAP, resulting in the formation of stearic acid due to the degradation of MgSt caused by neutralization of acidic CAP. FTIR microspectroscopy can be used to effectively identify the

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    Present address: Department of Biotechnology, Yuanpei University, Hsin Chu,Taiwan, ROC.

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