JULY 2012

Manufacture & Evaluation of Calcium + Vitamin D3 Chewing Gums

Introduction

With increasing life expectancy, osteoporosis is becoming a major global health problem. The magnitude of this disease has increased in the Middle East, where the prevalence of low bone mass is higher than in western countries. Many Middle-Eastern and East-Indian women residing in the United Arab Emirates (UAE) have a very conservative style of dress that covers most of the body when they are outside, limiting exposure to sunlight. Several studies have shown that women from the Middle East have low serum concentrations of 25-hydroxy vitamin D, mostly as a result of low vitamin-D intake and inadequate exposure to sunlight (1 - 6). Non-pharmacological intervention consisting in ensuring adequate calcium and vitamin-D intake through calcium supplements (0.5-1 g/day) and low doses of vitamin D (800 IU per day) reduces the risk of hip fracture in elderly women in nursing homes [7]. In a 5-year study [8], the authors concluded that supplementation with calcium-carbonate tablets supplying 1200 mg/d is ineffective as a public-health intervention to prevent clinical fractures in the ambulatory elderly population owing to poor long-term compliance.

Failure to follow through with a treatment decision is one of the biggest causes of unsuccessful medical care. Disease management in out-patients is mainly affected by patient compliance to the drug therapy, which in turn is governed by patient convenience. At present, different formulation options are available for various drugs, and hence, the decision is based on the most convenient dosage format for the patient, along with optimum therapeutic benefits. Direct-to-consumer marketing in recent years has created an empowered patient whose needs must be addressed by patient-friendly dosage formats that offer ease of administration and convenience. Medicated chewing gum is an example of such a dosage format, consisting in an active ingredient incorporated into a chewing gum released through the mechanical action of chewing. Nowadays, chewing gum is gaining attention as a very good vehicle for administering active ingredients in pharmaceuticals and nutraceutics [9]. It offers a highly convenient, patient-compliant way of dosing medications, particularly for people with swallowing difficulties such as children and the elderly. Chewing gum makes administration of drugs possible anywhere, anytime without simultaneous intake of water, which promotes very high patient compliance. Calcium deficiency is mainly found in children and the elderly, groups that also have difficulty swallowing tablets. As chewing gum is not meant to be swallowed, patient compliance increases especially in these age groups. Moreover, chewing gum does not draw any attention to the medication and therefore it does not stigmatise the patient [10], which is highly desirable for supplements like calcium and vitamin D3.

Therefore, this study was undertaken to investigate the potential of chewing gum in delivering calcium and vitamin D3 while targeting patient convenience and therefore improved patient compliance.

Materials and methods: Gum base was kindly gifted by CAFOSA gum, Spain. For drug and other excipients we have used high quality marketed preparations. Calcium and Vitamin D3 were used from crushed powder of Calcivyte Tablets, Vitane Pharmaceuticals, USA. Sorbitol was obtained from Sigma-Aldrich Chemie GmbH, Switzerland. Colour, flavour and vegetable oil used were high quality food products.

Methods

With a bit of trial and error, we have optimised the chewing gum formulation with respect to plasticisers, chewing mass and calcium + vitamin D3 content. For the optimised formulation, see Table 1.

Manufacture & Evaluation of Calcium + Vitamin D3 Chewing Gums

The required amount of the gum base, glucose syrup and plasticisers (vegetable oil and sorbitol) was softened at 70-80 °C on a hot plate. The softened gum mass was removed from the heat and mixed with aspartame and pre-soaked calcium powder with flavour and colour and thoroughly mixed. Finally the mass was cut and shaped to provide single doses of calcium and vitamin D3.

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