Mannitol crystalline

Multifunctional excipient composed of x-chitin and crystalline mannitol [55] The coprocessing of a-chitin with crystalline mannitol was investigated and found to significantly improve the performance and functionality of the obtained excipient when compared to individual components. a-Chitin forms nonhygroscopic (Fig. 2.43), highly compactable, disintegrable compacts when coprocessed with crystalline mannitol. 

The time needed to complete desorption is highly dependent on product formulation and drying temperature. Crystalline mannitol usually requires only a short secondary drying, because the amount of bound water is minimal. On the other hand, glass-like systems formulated with sucrose or lactose necessitate a prolonged secondary drying. 

Continue precisely as for triacetin, but since hexacetyl-mannitol (p. 142) is a crystalline compound, weigh out i o-i 2 g. of the finely powdered substance, either from a weighing-bottle, or by direct weighing in the flask A. The results are excellent. 

The 1995 Canadian and United States sugar alcohol (polyol) production is shown in Table 2. The market share of each is also given. Liquids comprise 48% crystalline product comprises 39% and mannitol comprises 13% of the polyol market. An estimate of total U.S. sorbitol capacity for 1995 on a 70% solution basis was 498,000 t. ADM, Decatur, lU., produced 68,200 t Ethichem, Easton, Pa., 13,600 t Lon2a, Mapleton, lU., 45,400 t Roquette America, Gurnee, lU., 68,200 t and SPI Polyols, New Castle, Del., 75,000 t (204). Hoffman-LaRoche, which produces sorbitol for captive usage in the manufacture of Vitamin C (see Vitamins), produced about 27,300 t in 1995. 

K. Izutsu, S. Yoshioka, and T. Terao, Effect of mannitol crystallinity on the stabilization of enzymes during freeze drying, Chem. Pharm. Bull. (Tokyo), 42, 5 (1994). 

Upon standing, the mother liquor deposited more allitol—some 3 g. after a period of two months. No crystalline material was obtained from the ethereal solution. We thus obtained from 100 g. of divinylglycol, 11 g. of D,L-mannitol and 15 g. of allitol. 

Sugihara and Schmidt49 reported the isolation of 2,5-anhydro-D-glucitol in crystalline form its preparation on a relatively large scale has been described in the patent literature,50 and consists in the thermal dehydration of D-mannitol. The process leads to the formation of 1,4-anhydro-D-mannitol, 1,5-anhydro-D-mannitol, 1,4 3,6-dianhydro-D-mannitol, and 2,5-anhydro-D-glucitol, which is isolated as the crystalline 1,3-O-isopropyIidene derivative (35). 

Anhydro-D-mannitol is also obtained by a novel route from 1,6-dibenzoyl-D-mannitol. When this compound is heated with p-tolu-enesulfonic acid in acetylene tetrachloride, it suffers partial dehydration and one of the products is a dibenzoyl derivative of mannitan. On debenzoylation of this substance it yields crystalline 1,4-anhydro-D-mannitol.67 The formation of dibenzoyl-1,4-anhydro-D-mannitol has involved the migration of at least one benzoyl group and Hockett and coworkers6 believe that the initial product is either 2,6- or 3,6-dibenzoyl-1,4-anhydro-D-mannitol. 

Crystalline 1,4-anhydro-D-sorbitol is of much more recent origin than 1,4-anhydro-D-mannitol, inasmuch as its preparation was first recorded in 1946.10 It was obtained by the restricted dehydration of D-sorbitol and has been given the trivial name arlitan. Two groups of workers simultaneously effected proof of its constitution. Hockett and coworkers11 treated the anhydride with lead tetraacetate and since its rate of oxidation coincided with that of ethyl D-galactofuranoside and since one molecular proportion of formaldehyde was formed, the authors concluded that the ring must involve Cl and C4 of a hexitol chain. Assuming that no other carbon atoms are involved, sorbitan is either 1,4-anhydro-D-sorbitol or 1,4-anhydro-D-dulcitol (Walden inversion at C4 of the sorbitol molecule). They therefore synthesized 3,6-anhydro-D-dulcitol (enantio-morphous with 1,4-anhydro-L-dulcitol) but found it to be different from arlitan. 

Dianhydro-n-mannitol or isomannide was first prepared many years ago by Fauconnier44 who obtained it by heating D-mannitol with hydrochloric acid. The dianhydrides of D-sorbitol and L-iditol were not prepared, however, until very recent times. Although isomannide is a crystalline substance forming well defined derivatives very little work has been carried out on it and its structure was not determined until 1945, but in that and the following years a flood of experiments having a... 

One of the dianhydrohexitols, B, was identified with l,5 3,6-dianhy-dro-D-mannitol (neomannide, see below), but the other two, A and C, remain of unknown structure. An interesting observation concerning the dianhydride A has been made.48 When l,6-dichloro-l,6-didesoxy-D-mannitol was treated with sodium methoxide a new crystalline dianhydrohexitol was obtained. This had m. p. 118-119° but showed la]D + 33.6°. It was therefore the enantiomorph of dianhydride A. Furthermore, when dichloro-didesoxy-D-mannitol is treated with sodium amalgam yet another dianhydride was isolated. This had m. p. 118-119° and fa]D + 93.6° and is doubtless identical with the /3-mannide of Siwoloboff.49... 

Small amounts of surfactants may be used to prevent aggregation of proteins and may enhance the refolding process when the dried protein dissolves. Buffers may also help to prevent aggregation of the dissolved drug. Similarly, polymers may be used as aggregation inhibitors or to form matrices. Chan et al. [86] prepared crystalline powders of recombinant human deoxyribonuclease with high fractions of sodium chloride. These powders were formulated as adhesive mixtures on lactose and mannitol and showed improved aerosolization behaviour compared to the pure protein. 

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