|Publication number||WO1997038740 A1|
|Publication date||23 Oct 1997|
|Filing date||14 Mar 1997|
|Priority date||18 Apr 1996|
|Also published as||EP0897304A1|
|Publication number||PCT/1997/4171, PCT/US/1997/004171, PCT/US/1997/04171, PCT/US/97/004171, PCT/US/97/04171, PCT/US1997/004171, PCT/US1997/04171, PCT/US1997004171, PCT/US199704171, PCT/US97/004171, PCT/US97/04171, PCT/US97004171, PCT/US9704171, WO 1997/038740 A1, WO 1997038740 A1, WO 1997038740A1, WO 9738740 A1, WO 9738740A1, WO-A1-1997038740, WO-A1-9738740, WO1997/038740A1, WO1997038740 A1, WO1997038740A1, WO9738740 A1, WO9738740A1|
|Inventors||Geoffrey G. Booth, Dwan F. H. Chowdhury|
|Applicant||Minnesota Mining And Manufacturing Company|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (4), Referenced by (1), Classifications (5), Legal Events (7)|
|External Links: Patentscope, Espacenet|
COMPRESSED ABSORBENT AGGREGATE
This invention relates to compressed absorbent aggregates which are suitable for thickening human excretion products, particularly urine.
BACKGROUND Stoma patients who have been provided with intestinal passage by surgery empty the contents of the intestine into containers. These containers are usually plastic bags which are attached directly to the artificial intestinal passage and sealed off as tightly as possible. The same applies to patients who, owing to urinary fistula or for other reasons, have been given an artificial urinary passage. These patients have to cope with the problem that the excretion emptied into the collecting bag is frequently liquid. Moreover, it frequently develops an unpleasant smell owing to the increasing formation of gas. As a result, both the patient himself and those in the surrounding area may be considerably disturbed and inconvenienced. The liquid character of the excretion products, as in the case of urine and intestinal contents, may be ofa very thin consistency. Such a person may have to empty or change his or her urostomy pouch several times per day and between changes the pouch will often contain a quantity of liquid which sloshes about when the person moves. This is embarrassing and raises doubts in the wearer's mind as to the security of attachment of the pouch to the body, even though the attachment may be quite secure.
For this increasing proportion of stoma patients, it is extremely desirable for the excretion products (contents of the intestine or urine) to be thickened by simple measures to a consistency which corresponds approximately to the consistency of wallpaper paste. Such thickening will prevent undesirable slopping of the excretion products but allow the contents of the collecting bag to be readily emptied thus allowing for re-use of the bag. Various proposals have been made to incorporate superabsorbent materials, such as sodium polyacrylate, into urostomy bags and similar containers. Examples of such materials are disclosed in US-A-4179367, GB-A-2268882, GB-A- 1595687 and EP-A-0138427. However, none of the materials has found widespread acceptance by stoma patients.
The present invention provides new compressed absorbent aggregates suitable for use in urostomy bags and the like. According to a presently preferred embodiment of the present invention there is provided a compressed absorbent aggregate comprising:
60 to 80% by weight superabsorbent
20 to 40% by weight microcrystalline cellulose; and optionally
0.1 to 10% by weight hydrophilic lubricant. The compressed absorbent aggregates may be in the form of tablets. This facilitates insertion into an ostomy bag, for example, via an integral addition port. The tablets are fast-disintegrating in the presence of aqueous media, generally taking from 1 to 10 minutes to disintegrate completely in the presence of sufficient water. The presence of the superabsorbent polymer promotes steady progressive thickening of the liquid into a gelled but flowable consistency without forming a stiff intractable gel. The thickened contents may be expelled from the bag via an integral valve, thus allowing for re-use of the bag.
DETAILED DESCRIPTION The main constituent of the aggregates of the invention is a superabsorbent.
Suitable superabsorbent materials are well known and generally comprise a water- insoluble but water swellable polymeric substance capable of absorbing water in an amount which preferably is at least 10 times the weight of the substance in dry form. Suitable superabsorbent materials are disclosed, for example in EP-A- 0138427. A preferred superabsorbent material for use in the invention is cross- linked sodium polyacrylate, such as the product commercially available from Allied Colloids under the trade name Salsorb 90. Salsorb 90 is available with a main particle size range of 100-850μm and as Salsorb 90 fines having an average particle size of about 150μm. Either material may be used, although the finer grade provides a smoother surface to tablets and slightly improved gelation performance in aqueous media due to its increased surface area. In general, a reduction in particle size below 150μm may improve some properties of the tablets while deleteriously affecting other properties, such as, hardness and gelation time.
Preferably the particle size is in the range 160 to 355 μm, more preferably 160 to
210μm. The superabsorbent is preferably present in an amount in the range 60 to 80% by weight of the aggregate, more preferably 65 to 75%, most preferably 67 to 72% by weight.
The aggregates of the invention also preferably comprise microcrystalline cellulose. Microcrystalline cellulose is an extremely compressible material. It is derived from a special grade of purified alpha wood cellulose by severe acid hydrolysis to remove the amorphous cellulose portions, yielding particles consisting of bundles of needle-like microcrystals. The majority of these microcrystals range in size from 1 to 10 microns.
Microcrystalline cellulose combines several properties ofa useful tabletting vehicle. These are filler, binder, disintegrant, lubricant and flow aid. While it is capable of producing very hard tablets, these tablets still are able to disintegrate rapidly in water due to swelling of the microcrystalline particles and destruction of the bonding forces holding them together. There are several particle sizes available, the choice largely dependent on the fluidity to be imparted to the formulation.
Microcrystalline cellulose is commercially available from FMC Coφoration under the trade name "Avicel". A preferred material for use in the invention is
Avicel PH101. The microcrystalline cellulose is generally used in an amount in the range 20 to 40% by weight of the aggregate, more preferably from 25 to 35%, and most preferably from 25 to 29% by weight of the aggregate.
When formed into a tablet the aggregates of the invention also preferably additionally comprises a hydrophilic lubricant. The lubricant helps prevent adherence of the granules to punch faces and dies used during tablet compression. In addition, it ensures smooth ejection of tablets from the die. Many known tabletting lubricants depend upon hydrophobic groups for their lubricant effect. However, it has been found that such lubricants have a deleterious effect on the disintegration and gelling properties of absorbent tablets and hydrophilic lubricants must be used in the materials of the invention. Suitable hydrophilic lubricants include polyethylene glycol (PEG), DL-leucine, glycine, sodium chloride, sodium benzoate, sodium stearyl fumarate, sodium lauryl sulphate. The preferred hydrophilic lubricant is polyethylene glycol grade 6000 (PEG 6000). The hydrophilic lubricant is generally used in an amount in the range from 0.1 to 10% by weight of the aggregate, more preferably 1 to 6% and most preferably 2 to 5% by weight.
The aggregates may include minor amounts of other excipients e.g. cosmetic additives such as colorants, deodorizers etc.
The compressed aggregates of the invention are conveniently in the form of tablets. The size and shape of the tablets may be varied. Generally, the tablets have a weight of from 1 to 5g. For example, 14mm round tablets provide a nominal weight of 1.5g per tablet and 23mm round tablets provide a nominal weight of 4g. The tablets preferably have a hardness (kp) of at least 5, more preferably at least 8, and an abrasion loss of no more than 2% by the test described hereinafter. Abrasion loss was measured on an Erweka tablet test machine Type TAD commercially available from Erweka Apparatebau GmbH. The machine was operated at a fixed speed of 25rpm and was equipped with an Abrasion Test Drum, 200mm in diameter and having internal paddle blades which carry the tablets to a certain height and then allows them to slide down, thereby causing them to rub together without hard impact.
The test procedure used samples of five tablets which were de-dusted and weighted (Wl). The weighed tablets were then placed in the test drum and allowed to rotate for five minutes. The tablets were then re-weighed (W2), having first removed any accumulated dust and results calculated in terms of percentage weight loss using the formula (W1-W2) x 100 ÷ Wl . This test is designed to determine the resistance of tablets to abrasion and shock likely to be experienced during manufacturing, packing, shipping and use.
The aggregates of the invention should preferably readily disintegrate in aqueous media. The time for complete disintegration in excess aqueous medium preferably is less than ten minutes, more preferably less than five minutes and most preferably less than one minute. In practice the aggregate will be subjected to progressive dilution with urine and should maintain an ongoing thickening action without forming a rigid gel (gel lock).
The aggregates of the invention may be prepared by blending the components of the formulation followed by compression. The components may be blended in a conventional mixing apparatus e.g. a Turbula T2C mixer. The abrasion loss and gelation performance of tablets have been found to be independent of blending times within the range of five to seventy minutes.
The blend of components may be compressed in conventional apparatus, such as tabletting machines. The compression dwell time has been found to significantly affect the properties of the compressed aggregate. In particular, abrasion loss is significantly reduced by employment of increased compression dwell time. For example, compression on a Manesty D tablet machine employing a turret equipped with 16 tooling stations operating at 17rpm, i.e. 272 tablets/minute, forms tablets having significantly reduced abrasion losses when compared to the same machine operating at 40rpm i.e. 640 tablets/minute. Many modern tablet machines are capable of operating at output levels of at least 80K to 100K tablets/hour, i.e. in excess of 1300 tablets/minute. The compression dwell time at such speeds is less likely to produce satisfactory tablets for use in the invention. The invention will now be illustrated by the following Examples. Unless otherwise stated all parts and percentages are by weight. Examples 1 to 3 The following formulations (%w/w) were prepared:
The formulations were blended and compressed into 1.5g tablets using a Manesty D tablet machine operating at an output level of approximately 270 tablets/minute. The machine comprised a turret equipped with 16 tooling stations and operated at 17rpm.
The tablets were examined and the disintegration/gelation performance examined by the addition of 100ml synthetic urine to three tablets at room temperature.
Example 1 produced a tablet having a pitted surface which crumbled on storage. Very fast disintegration (less than one minute) in synthetic urine achieved a gel of the required consistency.
Example 3 produced a good, stable tablet which disintegrated totally in less than ten minutes to achieve the required gel consistency.
Example 2 produced a good stable, tablet which achieved the required gel consistency following a somewhat longer disintegration time than that observed in Example 3.
Examples 4 to 9
Formulations were blended from a bulk mixture of 70 parts by weight
Salsorb 90 fines and 30 parts by weight Avicel PHI 01 and water soluble lubricants.
The individual lubricants were added in levels of 2, 4, 6, 8 and 10% by weight and compressed into tablets as in the previous Examples. The physical and gelation properties of the tablets were assessed. The lubricants used and results are reported in the following Table:
Examples 10 to 21 A series of tests were conducted to ascertain the effect of compression time, compression pressure and particle size of Salsorb on the properties of the tablets. The following formulations were used:
The components of each formulation were blended together for 7 minutes.
The formulations were compressed into tablets on the machine used in the previous Examples operated at different speeds. The hardness and abrasion loss of the tablets were measured and the gelation time determined following the addition of one tablet to 200ml of tap water and timing the period for disintegration. The results are reported in the following Table:
A further series of tests was conducted in which the formulations were formed into tablets using the machine of the previous Examples, operating at 17φm but varying the setting for compression pressure (IP 2P<3P<4P<5P<6P). The properties of the tablets were measured an results are reported in the following Table:
The results indicate reduction in machine speed, provides increased compression dwell time and generally results in reduced tablet abrasion loss. There is an optimum compression pressure giving the lowest abrasion loss and highest tablet hardness.
Additional tests were conducted using the same basic formulation as Examples 10 to 21 with the exception the Salsorb was sieved to produce fractions having a particle size of <150μm, <125μm and <90μm. Tablets were produced from the formulations in the tabletting machine operating at a speed of 17φm. It was found the reduction in particle size of Salsorb resulted in the following properties: improved smoothness of surface of the tablet; reduced abrasion loss; large increase in gelation time, and reduced hardness. Of the three size fractions tested, the coarsest size fraction gives the preferred balance of properties.
The performance of absorbent tablets was examined in synthetic urine formulation comprising an aqueous solution of urea and sodium chloride and minor amounts of other salts.
Tablets of Example 18 complying with formulations Al and A2 were tested as follows:
First, a tablet was dropped into a glass dish containing 100ml of synthetic urine. Gelation occurred for tablets of Al and A2 formulations within 90 seconds in the synthetic urine formulation.
Then, to determine minimum volume of synthetic urine required to cause gelation of one tablet glass dishes were prepared containing 50ml, 60ml, 70ml, 80ml, 90ml and 100ml of synthetic urine and one tablet introduced into each dish. For each tablet it was found that 60ml caused complete gelation with no free urine present. At >70ml the gel was less viscous with free urine present.
The normal rate of urine production in man is ~2ml/minute (120ml/hour) and thus there is a steady trickle of urine into the external urostomy pouch ofa patient. In order to mimic urine production/flow into a urostomy pouch two drip tests were conducted: First, a tablet was placed in a glass dish and synthetic urine dripped directly onto the tablet from a burette at a rate of one drop/second, equivalent to ~120ml/hour.
A second test was additionally performed. This test is identical to the previous test with the exception the synthetic urine was dripped into the glass dish to one side of the tablet. This was deemed to be a more realistic test since it is unlikely that urine will drip directly onto a tablet in a urostomy pouch.
In each test 60ml of synthetic urine was dripped into the glass dish containing one tablet.
Tablets of formulations Al and A2 gradually swelled as they absorbed the synthetic urine. After 60ml synthetic urine had been added a small part of the core of the tablets remained but this gradually disintegrated and gelled on standing. Thus, it can be expected that the tablets will perform effectively in a urostomy pouch.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|EP0138427A2 *||21 Sep 1984||24 Apr 1985||Personal Products Company||Compressed absorbent aggregate|
|GB2301350A *||Title not available|
|US4179367 *||10 Feb 1978||18 Dec 1979||Chemische Fabrik||Thickening urinary and intestinal tract excrement|
|US4273761 *||10 Apr 1978||16 Jun 1981||Nippon Kayaku Kabushiki Kaisha||Method of enhancing absorption of antitumor agent into gastrointestinal tumor site and orally administrable antitumor compositions therefor|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|EP1199102A1 *||9 Oct 2001||24 Apr 2002||B. Braun Medical||Superabsorbent tablet and uses thereof|
|Cooperative Classification||A61L28/0026, A61L28/0049|
|European Classification||A61L28/00H7, A61L28/00B8|
|23 Oct 1997||AL||Designated countries for regional patents|
Kind code of ref document: A1
Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE
|23 Oct 1997||AK||Designated states|
Kind code of ref document: A1
Designated state(s): US
|4 Dec 1997||DFPE||Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)|
|21 Jan 1998||121||Ep: the epo has been informed by wipo that ep was designated in this application|
|6 Oct 1998||WWE||Wipo information: entry into national phase|
Ref document number: 1997917531
Country of ref document: EP
|24 Feb 1999||WWP||Wipo information: published in national office|
Ref document number: 1997917531
Country of ref document: EP
|29 Jan 2002||WWW||Wipo information: withdrawn in national office|
Ref document number: 1997917531
Country of ref document: EP