a central aspect of the present invention is the heretofore unnoticed complex formation between polyesters and carboxyl - containing compounds . such complexes may be used to facilitate slow release of the carboxyl - containing compounds in a variety of contexts , one including a concommittance with polyester hydrolysis . polyesters specifically tested include polyglycolide , polylactide and poly ( d ) l - lactide - co - polyglycolide ). persons having ordinary skill in the art understand that other polyesters , including those of other alpha - hydroxy carboxylic acids such as , e . g ., alpha hydroxybutyrate and the like will form analogous complexes . carboxyl - containing compounds specifically found to bind polyesters include acetylsalicylic acid ( aspirin ); ( s )-(+) 4 - isobutyl - α - methylphenylacetic acid ( ibuprofen ), benzoic acid , salicylic acid , phenoxyacetic acid and phenylacetic acid . the present invention includes synthesis of a polyglycolide and aspirin composite in which aspirin molecules are bound to the repeating units of polyglycolide . experimental evidence shows that at least one aspirin molecule may be bonded to each monomeric unit of polyglycolide . this binding , when equal amounts of aspirin and polyglycolide monomeric units are used , is about 1 : 1 . a 3 : 7 ratio has also been prepared . of course , if less aspirin is used , the ratio may be decreased at will . a 1 : 10 ratio or even lower may be suitable for some purposes . the polyglycolide / aspirin composite ( pac ) releases aspirin molecules as polyglycolide is degraded . the aspirin molecules would be made available to be physiologically effective . this physiological effect will involve reducing or eliminating inflammation and / or pain . pac may be ingested or inserted close to the site of the pain origin in order to be more effective as well as to extend the effect over a longer period of time . substitutes for polyglycolide such as polylactide or other polyesters may be used : polymers rich in ester groups but not polyesters , e . g ., polymethylmethacrylate should bind aspirin and the like . however , because they are not readily hydrolysable or biodegradable , such polymer composites are viewed as of more limited use . likewise , in place of aspirin , other substances , particularly those bearing free carboxyl groups may be used . for example , phenoxyacetic acid , salicylic acid an benzoic acid all have been found to interact with polyglycolide . simple homologs and derivatives of aspirin , such as those having halogen , methyl , methoxy , nitro and like substituents on the phenyl or acetyl will also form analogous polyester complexes . the preparation of these or other composites is analogous to that of pac and the formation similarly monitored . polyglycolide , prepared as previously reported ( ginde et al ., pinkus et al . ), and acetylsalicylic acid ( 99 +%), both in fmely powdered form , were mixed intimately in the ratio of 58 . 0 g . to 180 g ., respectively corresponding to the repeating unit molar amount of polyglycolide (— ch 2 coo —) and molecular weight of acetylsalicylic acid ( c 9 h 8 o 4 ). the mixture was heated in a sand or oil bath until it melted to a clear liquid . the clear liquid was then allowed to solidify . measurements were made on this material . the 1 h nuclear magnetic resonance ( nmr ) spectrum pac ( fig1 ) showed that the peak for the ch 2 protons of polyglycolide originally at δ4 . 91 ( fig2 ) was missing except for a small residual and had shifted far upfield to about 2 . 36 ( a shift of about 2 . 6 p . p . m .) next to the acetyl ch 3 peak of acetylsalicylic acid at about 2 . 41 δ . this showed that the ch 2 protons of the polyglycolide were shielded by the aspirin molecules . a likely interpretation is that an aspirin molecule is anchored to each carbonyl oxygen of polyglycolide by hydrogen bonding with the carboxyl hydrogen so that the benzene ring π - electron cloud is above the ch 2 group , resulting in shielding and requiring a higher magnetic field to bring these protons into resonance . a 1 hnmr spectrum of acetylsalicylic acid ( fig3 ) shows that the acetyl ( ch 3 c ═ o ) and benzene ring proton signals ( at 2 . 35 and about 7 - 8 δ , respectively ) do not change position much even considering that the latter spectrum is in cdcl 3 whereas the former spectra are in a cdcl 3 / cf 3 cood solution because of the insolubility of polyglycolide in most solvents ( hariharan et al .). an infrared spectrum ( fig4 ) shows the two strong carbonyl stretching peaks expected for the acetyl ester group in aspirin and the ester group in polyglycolide at 1695 and 1751 cm − 1 and a broad band & gt ; 3000 cm − 1 indicating strong hydrogen bonding . a melting temperature (* t m )/ composition plot ( fig5 ) also furnishes evidence for the 1 : 1 ratio between each aspirin molecule and each glycolide repeating unit [—( ch 2 coo )—]. it can be noted that the minimum tm value is close to the 50 % mole ratio indicating also a 1 : 1 correspondence of molecules of aspirin to the polyglycolide repeating unit . as an example of the various possible ratios of polyglycolide - aspirin combinations , a 30 : 70 mole ratio of polyglycolide monomer : aspirin is described . polyglycolide and aspirin were finely powdered and weighed . polyglycolide ( 0 . 116 g , 2 . 00 × 10 − 3 mole ) and aspirin ( 0 . 84 g , 4 . 70 × 10 − 3 mole ) in a flask under an argon atmosphere were heated in an oil bath to a temperature at which the lower - melting aspirin melted and dissolved the polyglycolide . on cooling , the melt solidified . the solid was powdered . hydrolysis was carried out with samples of the 30 : 70 polyglycolide monomer : aspirin mole ratio and polyglycolide alone for comparison as a standard . samples of polyglycolide approximately 0 . 3 g ( table 1 ) were weighed and transferred into clean centrifuge tubes . distilled water ( 15 ml ) was added to each tube and the mixtures were shaken in a water bath / shaker at 22 ° c . for various periods of time when selected samples were removed and centrifuged for about 5 minutes . aliquots of the clear supernatant solution were taken for analysis . aliquots were titrated with 0 . 0923 n naoh solution , using bromphenol blue indicator , for the glycolic acid hydrolysis product . results are in table 1 . since varying amounts of sample and aliquots of hydrolysis solution were taken , the volumes of naoh used were normalized to 1 . 0 g of sample and 1 . 0 ml of aliquot by dividing by the weights of samples and volumes of aliquots to give a corrected volume of naoh ( table 1 ). for polyglycolide hydrolysis , the corrected volume of naoh used in the titration is plotted against time of hydrolysis in fig6 . after an initial release of acid , hydrolysis proceeds at a moderate rate with time . for hydrolysis of the polyglycolide / aspirin combination , results are plotted in fig7 . after an initial fast acid release , further release of acid product levels off and then increases for about 72 hours , after which release of acid product increases slowly with time to 120 hours . for a 90 : 10 ( asp : polygly ) combination ( tm = 123 - 125 ° c . ): for a 0 . 3004 g . sample shaken for 3 hours , a 9 . 5 ml aliquot required 1 . 1 ml of 0 . 0923 n naoh . when this volume of naoh is normalized to account for the weight of sample and volume of aliquot , the corrected volume of naoh is 0 . 39 ml per g . sample per ml . aliquot . this can be compared with the normalized volume of 0 . 12 ml of naoh required for the corresponding 3 hour hydrolysis of the 70 : 30 mole ratio combination , over a three - fold increase in the release rate on this basis of comparison . this shows that the rate of release of aspirin can be controlled by the mole ratio of the aspirin : polyglycolide combination . for the 95 : 5 ( asp : polygly ) combination ( tm - 123 - 125 ° c . ): for a 0 . 3009 g . sample shaken for 3 hours , a 9 . 5 ml aliquot required 1 . 31 ml of 0 . 0923 n naoh . when this volume of naoh is normalized to account for the weight of sample and volume of aliquot , the corrected volume of naoh is 0 . 46 ml per g . sample per ml . aliquot , an increase over the 90 : 10 combination . this is further evidence that the rate of release of aspirin can be controlled by the mole ratio of the aspirin : polyglycolide combination . it is evident that when aspirin is combined in a homogeneous manner with polyglycolide , release is substantially modified since although aspirin readily dissolves in water to the extent of 1 gram / 300 ml at 25 ° c ., for the 30 : 70 mole ratio polyglycolide : aspirin combination ( where aspirin is present to the extent of 88 % by weight ), only a small amount of aspirin and combined aspirin - glycolic acid is released even after 5 days of shaking a powdered sample with water . the rate of release can be increased by increasing the % of aspirin in the combination . using aspirin alone ( sample of 0 . 3019 g comparable to amounts used with polyglycolide combinations ), after shaking 3 hours with 15 ml of water , an aliquot of the solution ( 14 ml ) required 2 . 6 ml of 0 . 0923n naoh . on calculation , this corresponds approximately to the solubility of aspirin in water as expected . this contasts markedly with the slow release from the 30 : 70 mole % combination ( containing ˜ 88 % aspirin ). the trial runs involved only 0 . 1 g of polyglycolide in 15 ml distilled water . the hydrolysis for the recorded trials is explained here . the hydrolysis was carried out in a water bath / shaker at room temperature ( 22 ° c .). samples weighing approximately 0 . 30 g were weighed out into clean centrifuge tubes ( 1 ml ). each tube was then filled with 15 ml of distilled water . four tubes were prepared in this manner . they were labeled pg1 ( 48 and 72 hours ), pg2 ( 96 and 120 hours ), pg3 ( 24 hours ), pg4 ( 1 and 3 hours ). all the tubes were placed in the bath for their allotted times . from each tube , after centrifuging for about 5 minutes , an aliquot of about 7 . 0 - 7 . 5 ml in volume was taken . the aliquots were representative of the time that the sample was allowed to hydrolyze for . for example , pg1 was removed after 48 hours and a 7 . ml aliquot was removed and then titrated . pg1 was then put back into the bath for its remaining allotted time — 72 hours . then a second aliquot was removed and then titrated . the titrations involved the use of a 1 . 0 ml syringe to dispense the 0 . 0923 n naoh basic solution into the aliquots . since glycolic acid was the expected product of hydrolysis , an indicator was chosen to match its ph range to the pka of glycolic acid ( 3 . 83 ). bromophenol blue was chosen because its ph range is 3 . 0 - 4 . 6 . about three drops of indicator were added to the aliquots . the aliquots were titrated from a yellow color to the faintest tinge of purple . the procedure for the hydrolysis of the combination was essentially the same as for the polyglycolide . the amount of samples were the same as well as the amounts of water added and aliquots removed . time intervals were the same . fig8 and table 3 show a summary of the poly : asp hydrolysis data . note the nice straight line for the plot of mole ratio vs . normalized ( corrected ) volume of naoh per g of sample per ml of aliquot titrated . the rate of release can be determined from the polygly : asp mole ratio . ( this is for a three hour hydrolysis . further studies will be carried out for longer times and with other hydrolysis mixtures .) polylactide and copolymers of polylactide and polyglycolide are also used as biodegradable materials . in view of the success with the homogeneous dispersal of aspirin in polyglycolide , the dispersal of aspirin in polylactide and polylactide / polyglycolide copolymers was investigated . although a few references have appeared for the use of polylactide and its copolymers with polyglycolide for controlled release , none of these have incorporated aspirin according to the processes described herein . the reagents were commercially purchased compounds . the polylactide was about 96 % l - isomer . t m was determined to be about 138 ° c . the amount of polylactide used was based on the repeating unit (— chch 3 coo —) per molecule of aspirin . the aspirin ( acetylsalicylic acid or 2 - acetoxybenzoic acid ) t m was 138 - 140 ° c . the two components were mixed in powdered form in a flask protected by a drying tube in the amounts , 0 . 147 g ( 0 . 00204 mol ) polylactide and 0 . 353 g ( 0 . 00202 mol ) aspirin and heated in an oil bath until the mixture just melted to a clear homogeneous liquid , at which point the flask was allowed to cool to room temperature . the temperature was kept as low as possible and reagents were not heated any longer than necessary to liquefy them in order to avoid any possible decomposition . the solid product was powdered and t m determined to be 129 - 132 ° c . the poly [ dl - lactide - co - glycolide )] ( 65 : 35 ) ( i ) was a commercially purchased material . the mole ratio was based on the repeating unit , (— chch 3 coo —) 65 -(— ch 2 coo —) 35 assuming that each repeating unit hydrogen - bonds to two aspirin molecules or a ratio of aspirin : i of ( 180 × 2 ): 67 . 1 ( in grams ). the procedure was the same as that described above for polylactide . the two components were mixed in the ratio of aspirin ( 0 . 608 g , 0 . 00338 mol ) to i ( 0 . 138 g , 0 . 00206 mol ) or 0 . 00338 × 2 mol aspirin to 0 . 00206 mol of i or 3 . 28 aspirin : 1 . 00 mol of i . this mixture became a clear liquid with the oil bath at about 138 ° c . tm of the solid obtained after cooling was 128 - 131 ° c . other polylactide / polyglycolide copolymers are commercially available , such as poly ( dl - lactide - co - glycolide ) ( 85 : 15 ), ( 75 : 25 ), and ( 50 : 50 ). it is evident that similar combinations of these and aspirin may be prepared . based on the successful combination of aspirin and polyglycolide , the application of the method used was applied to ibuprofen as an example of another commonly used medicinal containing a carboxyl group . this experiment is described . two different brands of commercially purchased ibuprofen [( s )-(+)- 4 - isobutyl - α - methylphenylacetic acid ] were used , m . p . 51 - 53 ° c . polyglycolide was synthesized by a published procedure ( pinkus , a . g . et al . 1984 ), m . p . 212 - 214 ° c . the reagents in powdered form were mixed in the proportions , polyglycolide ( 0 . 116 g , 0 . 002 mol ) to ibuprofen ( 0 . 383 g , 0 . 00186 mol ) ( 2nd sample : 0 . 381 g , 0 . 00185 mol ) and heated in a moisture - protected flask by the procedure described above for polylactide . t m of the solid products obtained were 186 - 189 ° c . another medicinal that is commonly used for relief of pain and contains a carboxyl group is “ naproxen ” ( 6 - methoxynaphthyl - 2 - propanoic acid ). the melting point for the commercially obtained material was 157 - 158 ° c . however , when the same procedure was used with a mixture consisting of naproxen and polyglycolide , the mixture turned dark , an apparent decomposition . these were prepared by the same procedures as described above to demonstrate the generality of the method . among the carboxylic acids used were : benzoic acid , salicylic acid , and phenylacetic acid . it is thought that hydrogen - bonding of the carboxylate group of the carboxylic acid to the oxygens of the polyglycolide facilitates the combination . in the cases where the molar ratio of the acid to the repeating units of polyglycolide exceeds a 1 : 1 ratio for aspirin , additional hydrogen - bonding of the carboxylate group to the oxygens of the ortho - acetoxy group of aspirin can also take place . the following references are incorporated by reference herein for the reasons cited above . anon . 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the present invention involves an aspirin / polyglycolide complex , its preparation and use . the complex provides a stable aspirin source , slowly releasing aspirin by dissociation or during polyglycolide degradation in vivo .