J Pharm Pharmaceut Sci (www.cspscanada.org) 9(1):40-49, 2006

Investigation of vitamin and mineral tablets and capsules on the Canadian market

Raimar Löbenberg1, Wayne Steinke2

1Faculty of Pharmacy, University of Alberta, Edmonton, Alberta, Canada

2Select Health Centre Ltd., Edmonton, Alberta, Canada

 

Received 28 December 2005, Revised 21 January 2006, Accepted 22 January 2006, Published 10 February 2006

 

Corresponding author: Raimar Löbenberg, PhD, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. rloebenberg@pharmacy.ualberta.ca

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ABSTRACT  PURPOSE: The goal of this study was to investigate the disintegrating properties of tablets and capsules containing minerals and vitamins commercially available on the Canadian market and to review their label information. METHODS: The labels were examined for product-related information. The first disintegration test stage was performed using Simulated Intestinal Fluid (SIF) pH 6.8 for 20 minutes. Products which did not disintegrate were further investigated using USP disintegration conditions for dietary supplements. RESULTS: The provided label information is difficult to understand and in some cases pseudo-scientific. Thirty out of thirty-nine tablets and six out of ten capsules had a Drug Identification Number (DIN). Twenty-one of thirty-nine tablets and four out of the ten capsules did not disintegrate within 20 minutes. Using the USP disintegration conditions for dietary supplements nine tablet products did not fully disintegrate but all capsules passed the test. None of the three “time-released” products disintegrated under the applied conditions. CONCLUSIONS: Industry should follow already existing label recommendations more closely to allow the consumers to make an informed decision on their products by providing only essential information rather than using pseudo-scientific terms. The results of the disintegration study indicated that disintegration, one of the most basic quality control parameters, is still a concern for dietary supplements.

 

INTRODUCTION

Absorption of minerals, vitamins, drugs or food is a complex process. It can be generalized as passive absorption via a paracellular pathway, facilitated transport through membranes via transporters and active energy consuming transport mechanisms (1, 2). In the case of facilitated and active transport, the uptake mechanism can be specific to individual substances or to substance classes e.g. ions, amino acids, peptides or carbohydrates (3, 4). Absorption of calcium for example depends on the location within the gut (5). In the duodenum it happens via an active transport mechanism, while in the jejunum and ileum calcium is absorbed via passive diffusion. The extension of the active calcium uptake is greater as compared with the passive diffusion. In the duodenum, calcium enters the cytoplasm of enterocytes through a calcium channel ECaC2 (6). In the cytoplasm, a carrier protein called “calbindin” transports calcium to the basolateral membrane where it is pumped out of the cell via a calcium-ATPase and becomes systemically available. The availability of calbindin depends directly on vitamin D. Another example for partially localized mineral uptake is iron. Efficient absorption of inorganic iron requires an acidic environment due to the pH dependent solubility of iron (7). Drugs, such as antacids, proton inhibitors or excipients, which interfere or neutralize gastric acid secretions, may therefore, interfere with iron absorption. An acetic pH condition is only in the stomach and in the beginning of the duodenum before bile, and pancreatic secretions neutralize gastric fluids (8). Alternatively, organic bound iron is absorbed by endocytosis of hemoglobin or myoglobin by the enterocytes. This process is not limited to acetic environments and can take place throughout the gut. However, available supplements contain inorganic iron. An example of a specialized absorption of vitamins is cobalamin (Vitamin B12). The absorption depends on the availability of an intrinsic factor secreted by the stomach (9). Both molecules bind to each other to form a complex that can bind to specific receptors in the brush border of the intestine and are absorbed (8). The given examples clearly show that the absorption of minerals and vitamins is a complex process which involves in some cases specific transporters. Furthermore, for certain minerals or vitamins the absorption via active transport might be limited to absorption windows, favourable pH values, the presence of transporters or may depend on the availability of co- or intrinsic factors.

      Active ingredients can only be absorbed if they are released into solution from the dosage form. Disintegration is the first step in this process for immediate release dosage forms. The goal of this study was to investigate the disintegrating properties of tablets and capsules containing minerals and vitamins commercially available on the Canadian market and to review their label information.

 

Materials and Methods

Products where purchased from commercial outlets or received from professional centers and are listed in Tables 1 and 2.

 

Table 1. Tested Mineral and Vitamin Tablets: The front label information is the information which can be seen together with the product name. DIN is the drug identification number, Yes or No indicate if the product had a DIN, Stage 1 and 2 refers to the performed disintegration tests, + fully disintegrated, - not fully disintegrated, +/- not all units disintegrated but test was passed, - & - controlled release dosage form did not disintegrate within 30 minutes or 90 minutes. Other label information refers to additional text which was found on the label to describe the product.

Brand/Product
Manufacturer

Front label information

Units DIN

Lot #

Stage 1
Stage 2

Directions

Other label
information

Mel-Vita

Melaleuca  Inc. Idaho Falls, ID

 

Multivitamin & Multimineral Supplement

60

Yes

14005

+

 

For therapeutic use only
To be taken as supplement with meals
Adult dose above 34 kg 2 tablets per day

This unique formulation has 15 vitamins and minerals with the established Canadian R.D.I. providing the nutrients your body needs for optimum health

Cell-Wise

Melaleuca Inc.

Idaho Falls, ID

Vitamin E, C, Zinc
Beta Carotene, Selenium

60

Yes

 

13029

-

+

Tablets to be taken with  meals

For adults only
2 tablets per day

 

Contains only the  finest-quality ingredients in a balanced formula to complement your daily fruit vegetable and whole grain in take

Proprietary formula excusive to Melaeuca

Right Choice A.M. Multi Formula
Body Wise International LLC,  Tustin, CA

Now with Pycnogenol

Dietary Supplement

90

No

402113

+

Take three tablets with your morning meal

Pycnogenol is registered trademark…

Right Choice

Body Wise International LLC,  Tustin, CA

P.M. Multi Formula
Now with Pycnogenol

Dietary Supplement

90

No

403011

-

+

Take three tablets with your evening meal

 Dietary Supplement

Pycnogenol is registered trademark…
Krebs Cycle Chelated Mineral Replenishment factors are uniquely formulated

Centrum

Whitehall-Robison Inc.
Mississauga, ON

Centrum Multi Vitamin Multi Mineral Formula

New Formula

100 Yes

321461

+

1 tablet daily

 

Central-Vite Forte, Safeway Select
Safeway Canada

Calgary, AB

 

High potency multivitamins and minerals forte formula,

Essential vitamins and minerals, now with lutein

100 Yes

311230CS6

+

Take one tablet daily with a meal or as directed by a physician or healthcare practitioner
For therapeutic use only

Made to US-Pharmacopeia quality, purity and potency standards. Laboratory tested to dissolve within 60 minutes

one tablet daily Adults

Safeway Canada

Calgary, AB

 

24 vitamins and minerals  & beta carotene,
Scientifically balanced formula

90

Yes

 

3L0580BYP

+

Take one tablet daily with a meal or as directed by a physician or healthcare practitioner
For therapeutic use only

Made to US-Pharmacopeia quality, purity and potency standards Laboratory tested to dissolve within 60 minutes

One A Day Advance Adults

Bayer Inc. Toronto, ON

24 vitamins and Minerals, Feel your best,
Advance, Adults Formula

 

90

Yes

310120A6Q

+

 

One tablet  daily

Scientifically balanced formula for adults

24 Vitamins and Minerals

Advanced formula

London Naturals Multi Vitamin Iron Free

London Drugs

Richmond, BC

Multivitamin and mineral complex, with extra Bs and lipotropics one per day

60

No

 

66901

+

1 tablet per daily, or as directed by professional


For therapeutic use only

Certified Guaranteed Excellence

One Tablet Daily
London Drugs Limited

Richmond, BC

London Drugs
Scientifically balanced formula, Adults,
23 vitamins and minerals & Beta Carotene

90

65387

Yes

+

Take 1 tablet daily, or as directed by a physician
 For therapeutic use only

 

Basic 3

Atkins Nutritionals Inc.

Ronkonkoma, NY

Atkins

Essential Nutrients

Maintains Normal Blood Sugar Level, Advanced Antioxidants

90

No

 

0497B4

-

+

Take three tablets daily, for adult use only
For therapeutic use only

Absorb Best TM

Advanz
Holista Health, Burnaby, BC

Most advanced complete daily nutrients from A to Z
Extra Strength Daily
Multivitamin & Multimineral with iron

Holista

90

Yes

60040

+

One Tablet daily or as recommended by a physician

 

Usana Health Science Inc.

Salt Lake City, UT

Essentials Multi Mineral

84

Yes

 

9961

+

Information not available

Laboratory tested for guaranteed quality
Meets specifications for potency, uniformity, and disintegration, as appropriate

Kirkland Signature Formula Forte
Cosco Wholesale Canada, Ottawa

With Lutein

30 essential multivitamins with beta carotene

365

4BA2002

Yes

-

-

Take one tablet daily with meal

For therapeutic use only

Other ingredient: Lutein

Multiple Vitamins

Pharmetics Inc.

Laval, QC

Plus iron, Tanta

100 Yes

 

43608A

+/-

 

As vitamin and iron supplement

Take one tablet with a meal or as directed by a health professional

 

Ultimate One for Men
Active

Nu Life, Richmond Hill, ON

Multi vitamin and mineral, Active

60

0045K3

Yes

-

-

Take 1 caplet daily, with a meal or as directed by a health practitioner
For therapeutic use only

In a specially designed base for man

Ultimate One for Women
Active
Nu Life, Richmond Hill, ON

Multi vitamin and mineral, active

60

Yes

 

0934A3

-

+

Take 1 tablet with a meal or as directed by a health professional
For therapeutic use only

In a specially designed base for woman

Wampole
Multi Vitamins & Minerals

Wampole Brands Inc. Toronto, ON

Fortified with 31 Vitamins Minerals and Nutrients with Lycopene & Lutien

180

566878

No

-

+

Take 1 tablet with a meal or as directed by a health professional
For therapeutic use only

 

100 % Natural Source

Complete Multi-Adult Tabs

Wampole

Toronto, ON

Complete Multi-Adult
29 Essential vitamins and minerals

100

539997

Yes
-

+

One tablet daily with food or after meal

For therapeutic use only

Naturally Canadian since 1893

Trophic

Trophic Canada LTD Penticton, BC

Multiple Vitamins & Minerals

90

Yes

 

96905B

-

-

Take 1 tablet daily or as directed by physician
For therapeutic use only

Purely, Naturally, All Canadian
Manufactured under the unique Albion laboratories process whereby the minerals are chelated by amino acids, peptides and polypeptides

Sisu Only One

Sisu Enterprises Co. Inc.

Burnaby, BC

One a day multi vitamin and mineral

60

Yes

40089

-

-

 

Take 1 tablet daily with a meal or as directed by a health professional
For therapeutic use only

 

Super Multi Plus Iron

Natural Factors
Coquitlam, BC

All you need is one
Multi vitamin and Mineral Complex for Everyone

90

Yes

72290

+

1 tablet daily or as directed by a health practitioner
For therapeutic use only

 

Multidyn

Professional Health Products

Innisfail, AB

Professional Health Products

90

Yes

 

F3942

+

For therapeutic use only
One tablet  with each meal

 

Super Swiss One "50"

Swiss Herbal Remedies LTD

Richmond Hill

Multi Vitamin & Mineral

With Lutein, Natural Sources

60

Yes

 

2652

-

- & -

Adults take one caplet daily

For therapeutic use only

Time-release caplets are designed to gradually release their contents over a prolonged period of time

Swiss One "80" Swiss Herbal Remedies LTD

Richmond Hill

Hi Potency Multivitamin

One per day
With HVP Chelated minerals, time-release

60

Yes

1741

-

- & -

Adults take one caplet daily

For therapeutic use only

Time-release caplets are designed to gradually release their contents over a prolonged period of time

Quest Exta Once A Day

PanGeo Health Brands Inc.

Vancouver, BC

Multiple Vitamins & Minerals
Premium Quality

60

Yes

517780

-

+

One tablet with morning or noon meal
For therapeutic use only

Manufactured in Canada according to good manufacturing practices…

Multigenics Without Iron

Megagenics Inc. San Clemente, CA

Optimum Multiple Vitamin/Mineral Plan Fast release tablet

Dietary Supplement

Metagenics: Genetic Potential Through Nutrition

90

No

 

93072

-
+

Servings size 6 tablets with meal

Multigenics without iron is a unique vitamin and mineral formula designed for optimal disintegration and digestibility… Genetic potential through nutrition

Multigenics

Megagenics Inc. San Clemente, CA

Optimum Multiple Vitamin/Mineral Plan Fast release tablet

Dietary Supplement Metagenics: Genetic Potential Through Nutrition

90

No

 

103088

-

+

Servings size 6 tablets with meal

Selected nutrients to support liver and adrenal function
Genetic potential through nutrition

Mega Men

General Nutrition Canada, Mississauga, ON

GNC, Multi Vitamin & Mineral, Timed Release

180 Yes

 

568152

-

- & -

Take two per day or as directed by your physician

For therapeutic use only

Timed Release, multivitamins & Minerals
Now with ChloraSeal coating

Centrum Forte
Whitehall-Robison Inc.
Mississauga, ON

High potency Multivitamin Multimineral Formula
New Formula

60

Yes

316153

+

1 Tablet daily
Therapeutic use only

Complete from A to Zinc

Basic Vita-Vim Jamieson Laboratories, Toronto, ON

20 Minerals, Vitamins & Nutrients

Level 1 potency multivitamin

90

Yes

 

373212

+

Take one caplet daily with a meal

For therapeutic use only

No sugar, No Salt, No Starch, No Gluten 

Guarantee of Absolute Purity & Full Potency

Mega Vita Jamieson Laboratories, Toronto, ON

37 vitamins, Minerals & Nutrients

Level 4 Potency Multivitamin

60

Yes

 

381678

-

+

Take one caplet daily with a meal

For therapeutic use only

No sugar, No Salt, No Starch, Gluten free

Essential Balance

Pharmavite Corp.

Thornhill, ON

Nature Made Multivitamin & minerals

With selenium & folic acid

For adults
USP Quality

100 Yes

NK20393

-

+/-

As a vitamin and mineral supplement for adults take one tablet daily with a meal , supplying
For therapeutic use only

 

Ultra Balance III Douglas Labs
Pittsburgh, PA

A Vitamin & Mineral Supplement
For therapeutic use only

180 Yes

427504

-

+/-

Take 6 tablets daily (3 times 2) or as directed by your health care practitioner

 

Multi Vite 109

Seroyal Int Inc. Toronto, ON

Multiple Vitamin-Mineral Supplement

Genestra Brands

90

Yes

 

754203

+

For  therapeutic use only

Take one tablet two times daily with meals or as recommended by your health care practitioner

Hypoallergenic product

 

 

 

 

Exact

Loblaws Inc, Montreal, QC

Multivitamins

8 essential vitamins

for adults

no preservatives added

250 Yes

 

F05301

+

Take 1 tablet daily with a meal or as directed by a health  professional

For therapeutic use only

Trust Exact quality

Exact
Essentra Forte
Loblaws Inc, Montreal, QC

Vitamins & Multiminerals
high potency formula with lutein

100 Yes

 

F05770

+

Take 1 tablet with a meal or as directed by a health practitioner

 

Multi+

Ehn Inc, Toronto, ON

Complete, high potency Multi-Vitamin & Bioactive Mineral Formula

60 DIN pending

 

30437

-

+

Take two to four tablets daily


For therapeutic use only

Contains no artificial color, flavours sweeteners or preservatives, corn, diary, egg, whet , soy or animal products

Omnivite
Omnivite Nutrition

Portland, OR

With iron dietary multi vitamin-mineral supplement

180 No

 

0652304

+

As a dietary supplement, Adults take 2  tablets 2-3 times per day after meals

2-4 tablets per day provide optimal Daily supplementation to a well rounded whole foods diet and proper lifestyle, 6 tablets provide high level supplementation for chronic malnutrition, high stress or athletes

This product is low allergenic

 

 

Table 2. Mineral and Vitamin Capsules: The front label information is the information which can be seen together with the product name. DIN is the drug identification number, Yes or No indicate if the product had a DIN, Stage 1 and 2 refers to the performed disintegration tests: + fully disintegrated, - not fully disintegrated, +/- not all units disintegrated but test was passed, - & - controlled release dosage form did not disintegrate within 30 minutes or 90 minutes. Other label information refers to additional text which was found on the label to describe the product.

Brand/Product Name
Manufacturer

Front label information

Units DIN

Lot #

Stage 1

Stage 2

Directions

Other label information

 

Multi-encap
Thorne Research Inc.
Dover, IH

Thorne Research
without copper and iron

180

Yes

2042040

-

+

For Adult therapeutic use only

 

 

 

Nutri-plex
NaturPharm Inc. Toronto

Daily Multi-Vitamin Mineral Formula Hypoallergenic, Iron free

Blending tradition with Science

180

Yes

D0011

-

+

1 capsule 3 times daily with meal or as recommended by a health care practitioner

Contents are free of all artificial ingredients, preservatives, additives and common allergens

 

Multi IIs
Tyler Holdings Surrey, BC

New size, smaller, easier to swallow capsules Selekta

360

Yes

030984

-

+

Vitamin and mineral supplement for adults
For therapeutic use only

Take two capsules three times daily or as recommended by physician

This product is dispensed exclusively by health care professionals
Contains no chemical binders, fillers, coatings or allergenic additives

 

Super Orti Vite
Seroyal Int. Inc., Toronto, ON

Vitamin Mineral Supplement 128
Genesta Brands

120

Yes

0122304

-

+

For therapeutic use only

Take two capsules two times daily with meals or as recommended by your health care practitioner

Quality assurance: Safety-sealed for your protection

Hypoallergenic Product
Ideal for vegans

 

Ultra Preventive III Capsules

Douglas Laboratories
Pittsburgh, PA

A low allergenicity dietary supplement

180

No

0645304

+

As dietary supplement, adults take 6 capsules daily or as directed  by physician This product is best taken with meals

Meets Douglas Laboratories Spec [#7564]
Conforms to USP<2091> for weight
Meets USP<2040> for disintegration

 

Vital Life

Multivitamin Complex

Dietary Supplement

60

No

7430

+

As a dietary supplement; take one capsule daily with food or as directed by a physician

High bioavailability, allergen free; All ingredients are the highest quality and purity available Variation of product color may occur

 Mega Multi

GNC Pro Performance

Elite series

Superior multivitamin & Mineral Formula, rich in antioxidants, fast absorbing capsules

180

Yes

577613

+

Adults take 6 capsules daily, for therapeutic use only

Vitamin and mineral supplement and source of ubiquinone

Selekta Multis

Without copper

NA

NA

030983

+

Information not available

 

Ultragenesis

Without iron or copper

Comprehensive Multi 180 Vitamin

180

No

03295

+

As a dietary supplement, take 3 capsules two times per day or as directed by your health chare practitioner

Comprehensive multivitamin and mineral formula with phosphorylated forms and ratio balanced B vitamins
A broad spectrum of essential nutrients, along with fully reacted amino acid chelates

Solaray

Spectro Multi-Vita-Min

Natural beta carotene complex in a base of Siberian ginseng
Iron Free

100

Yes

082601

+

For therapeutic use only, take 1-2 capsules 2 time daily take with meals or glass of water

 

 

      The disintegration was determined using a disintegration tester ED 2L (Electrolab, Mumbai, India) which complies with USP <701> standards (10). The test units were inserted into the observation cylinder and the basket assembly was attached to the test apparatus. The appropriate immersion medium was filled into each beaker, and the test was started immediately after the basket assembly was attached.

      The test was performed using Simulated Intestinal Fluid (SIF) USP 28 pH 6.8 without enzymes and a test time of 20 minutes was applied. Products which did not disintegrate were further investigated using the conditions outlined in chapter <2040> (11). Briefly: for tablets, water was used as an immersion fluid, and the test duration was 30 minutes. If capsules were investigated, 0.05 M acetate buffer pH 4.5 was used as immersion fluid, and the test duration was 45 minutes. Disks were used in these tests. Products which claimed a “time-released” mechanism were included in the disintegration test. Here it was expected that the product will not totally disintegrate within the test duration. Time-release products were then additionally tested for 90 minutes in pH 6.8 without disks.

      The acceptance criteria for a successful test are the same for pharmaceutical and nutraceutical preparations. If all six units disintegrate, the test is passed. If one or two units do not fully disintegrate, then twelve additional units are tested. Only two units out of the total of eighteen tested units are allowed to fail complete disintegration.

 

Results

Thirty out of thirty-nine investigated tablet products had a Drug Identification Number (DIN). Six out of ten capsule preparations investigated had DIN numbers. The DIN number indicates that the product is registered with Health Canada. The product must meet quality and safety requirements set by the regulatory agency. The examination of the product labels showed that thirty-five out of forty-eight products used the term “For therapeutic use only”. These products had a DIN except for two products. Only two products claimed that they meet pharmacopeial quality standards (USP) for disintegration. Two products claimed to meet “US-Pharmacopeia quality, purity and potency standards.” One product claimed “optimal disintegration”, another that it was “manufactured according to Good Manufacturing Practices (GMP).” One product claimed that it “meets specifications for potency, uniformity and disintegration as appropriate.” However no specifications of “appropriate” were given. Other companies used terms of more general and informative character to describe their product: “New Formula”, “24 Vitamins and Minerals”, “No artificial flavours, no gluten, no lactose, no soy, without beta-carotene”, “time-released”, “Unique formulation”, “…established Canadian R.D.I. providing the nutrients your body needs for optimum health.” Other label claims included: “Scientifically balanced formula – release assured”, ”Contains only the finest quality ingredients”, “Purely, Naturally, All Canadian”, “Certified guaranteed excellence”, “Most advanced complete daily nutrient from A to Z…”, ” Guarantee of Absolute Purity & Full Potency”; however, there was no additional information available to support such claims. For example, which scientific dietary schedule has to be followed so that the supplement will have a balanced effect? Who certified the excellence? Which method assures the release? How is “Absolute Purity and Potency” defined? Furthermore, we were not able to define the following label statements:  “level 4 potency Multivitamin”; the term “level 4 potency” did not produce any results in a Medline search. A “Google” search only brought up WebPages which refer to the manufacturer; however, the scientific meaning of the term could not be clarified. A similarly unclear term was “bioactive mineral.” One product claimed “maintains normal blood sugar level” and this product had no DIN number such that it was not clear how this claim was supported by the product. Another curious claim about the product quality was “High bioavailability, allergen free; all ingredients are the highest quality and purity available. Variation of product color may occur.” If only the highest quality of ingredients is used, then obvious variations in color should not occur. The information “once a day” or “only one” was not considered as a sufficient statement that the product has any kind of time-release mechanism. Such statements were considered to reflect the appropriate daily dose and not any formulation aspects of the product. Only three products clearly stated that they have a time-release mechanism.

      The disintegration study was performed in two stages. In stage one; we investigated the disintegration of the tablet products at pH 6.8 in simulated intestinal fluid (SIF) without enzyme for 20 minutes. The test was performed without the use of the disks, eighteen out of thirty-six tablet formulations did not disintegrate according to the test criteria. Three “time-release” products which were also tested did not disintegrate. Four out of the ten capsule products did not pass the first disintegration test level. In summary, twenty-five products out of forty-six products which should have disintegrated failed the test.

      In stage two of our study, we applied the test conditions according to the USP chapter <2040> for minerals. Here the use of a disk in the observation cylinder is allowed. We only investigated products which had failed test stage one. Seven out of the twenty-one tested products did not fully disintegrate. Four products did not pass the test. All capsule products passed the disintegration test.

Five of seven products which failed complete disintegration recommend one tablet daily but none of these products claimed any extended release mechanism. The other two products recommended two and six tablets as daily doses.

      The three controlled release products did not disintegrate in stage two and were further investigated by performing an additional test for 90 minutes in SIF without the use of disks. None of the test units disintegrated within 90 minutes. However, it was clearly visible that surface erosion happened under both test conditions, indicating the presence of a time-release mechanism. Both disintegration conditions eroded the tablet surfaces similarly (visual observation).

 

DISCUSSION

All investigated products were combination products containing a variety of different ingredients. Only in very few cases the combination/formula could be traced to dietary schedule: “This unique formulation has 15 vitamins and minerals with the established Canadian R.D.I. providing the nutrients your body needs for optimum health” However, one has to know that RDI stands for “Recommended Daily Intake”. In many cases it was rather difficult to identify or to differentiate the product name from the brand name. Additional disturbing factors were highlighted “buzz words”, “New Formula”, “Active”. Such information has more advertisement character and should be avoided on the front of the label. The font sizes of some labels were rather small due to the limited space and of the long ingredient lists and other additional information given. Information on quality standards and standardization were only found on four products which used recognized USP standards as reference. However, plenty of self-advertisement and pseudo-standards were found on the product: “Manufactured in Canada according to good manufacturing practices (GMP)” However, GMP manufacturing does not guarantee drug release or disintegration; it guarantees proper process validation and documentation. Industry should follow already existing label requirements to help consumers to have all required information easily readable on the label. Only this will ensure that consumers can make informed choices.

      The USP 28 lists standard test methods for the quality of oral dosage forms. They are divided into different categories: performance test for oral drug products (Pharmaceuticals) (12), and performance test for dietary supplements (13). The different test methods are listed in Table 3.

      The characterization and quality control of pharmaceutical dosage forms is much more closely controlled compared to supplements. Drug release or dissolution requirements are core tests for the in vitro evaluation of pharmaceutical products.  There are no dissolution requirements specified for most minerals and vitamins. Therefore, disintegration was adapted as an easy and cheap test to have at least one quality control parameter for the dosage form. The chapters <701> (10) and <2040> (11) describe the disintegration of tablets and capsules for pharmaceuticals and dietary supplements respectively. The test apparatus is the same. However, different conditions are applied.

 

Table 3. Comparison of the performance test scheme recommended by the USP 28 for pharmaceuticals and dietary supplements. The <number> indicates the USP general chapter.

Pharmaceuticals

<301> Acid-Neutralizing capacity

<701> Disintegration

<711> Dissolution

<724> Drug release

<785> Osmolarity

<905> Uniformity of Dosage Forms

<1087> Intrinsic Dissolution

<1088> In vitro and in vivo Evaluation of Dosage Forms

<1090> In vivo Bioequivalence Guidance

<1216> Tablet Friability

 

Dietary Supplements

<1216> Tablet Friability

<2040>Disintegration and Dissolution of Nutritional Supplements

<2091>Weight Variation

<2750>Manufacturing Practices of Dietary Supplements

 

      The present study showed that the test duration and presumably the use of disks in the observation cylinder had an important impact on the ability of products to pass the disintegration test. At one test condition eighteen immediate release products failed, at the other only four products failed. The results indicate that disintegration is still a concern for dietary supplements.

      However, if a vitamin or mineral is poorly soluble or its dissolution is slow, then dissolution and not disintegration is the most critical parameter. Yet, it has to be pointed out that a product which fails disintegration will presumably fail dissolution criteria. Furthermore, if a mineral has to be absorbed within an absorption window and the dosage form does not release its content in a timely manner, then the therapy might be compromised or fail. An extended release dosage form on the other hand only releases parts of its total content at the absorption window like the duodenum and releases most of its dose in the jejunum, ileum and colon. This might cause a therapeutic failure due to insufficient absorption of some minerals or vitamins in deeper segments of the gut. Consequently, extended release dosage forms must show scientific evidence that the intended mineral or vitamin doses can be absorbed throughout the gastrointestinal passage.

      A recent study by Kamba et al. investigated the mechanical forces applied in the disintegration apparatus. (14) A tablet by itself hits the screen of the basket-assembly with a force of 0.19 N. The disk forces on the basket were reported as 0.31 N. This shows that a tablet might undergo two defined impulsive forces in the basket assembly: one when the disk hits and one when it hits the basket screen while the basket-rack assembly is moving up and down. Such forces might apply to the dosage form for each movement cycle of the basket assembly. The disintegration of the time-release products with and without disk showed that fluid forces combined with impact forces of the disks can increase the disintegration.

      Motility forces in the human intestine were reported to be up to 1.2 N. (15). The reported motility forces are for healthy humans. Recent studies by Aytug et al. (16) have shown that gender and menstrual cycles have an influence on motility pattern. Furthermore there are several diseases which impact motility like Parkinson’s disease, diabetes mellitus and thyroid diseases. (17) Therefore, many patients which have such diseases and take mineral supplements might have compromised motility. This might influence the disintegration of the administered dosage form. The general question which this study cannot answer is how therapeutically relevant are the reported results? However, the results show that there are products on the market which do not meet basic quality control measurements. Such products, and those needing higher mechanical forces to disintegrate (stage two in the present study), might therapeutically fail in patients due to insufficient motility forces, ultimately this applies to capsules and tablets.

      The new Heath Canada regulations for Natural Health Products, under which minerals and vitamins are regulated, need to clarify and outline guidance criteria for quality standards of minerals and vitamins. Only recognized test methods should be allowed to be used on the label. Health professionals, the industry and the consumer need to know how to identify a qualitatively acceptable product from a product with unknown quality. Meaningful disintegration standards accompanied with dissolution criteria are needed. Only this will ensure therapeutically efficacious dosage forms.

 

Conclusions

This study showed that there are products sold on the Canadian market which use statements on their label which are difficult to define. However, such terms and statements seem to be used to add pseudo-scientific and unjustified value to the product; such statements should be avoided. Only recognized test methods should be used on the labels. Dosage form and active ingredients need to be matched with their intended therapeutic use to ensure that the active is released at it site of absorption. Today’s customers cannot assume that the product they buy will have an acceptable quality with regard to the disintegration behaviour.

 

References

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