Lactose relative humidity

The range of application of shear cell testing methodology is seen in Tables 2-6. Table 3 relates the flow properties of mixtures of spray-dried lactose and bolted lactose. These mixtures, in combination with the excipients tested, cover a broad range of flow. Tables 4 and 5, for example, show lot to lot variations in the flow properties of several materials, and Table 6 shows the variation in flow properties of bolted starch, sucrose, and phenacetin at different relative humidities (RH). Figure 8 presents the yield loci of sucrose at four different consolidation loads. Also shown in the figure are the shear indices determined at each consolidation load. 

The reaction of neomycin with many compounds has been described in Section 3, hence numerous reports of neomycin incompatibility may be expected. Dale and Rundman have extensively reviewed the compatibility of neomycin with substances that may be encountered by the formulation pharmacist. Kudalker et al 03 have described the incompatibility of the antibiotic with rancid oils, and the incompatibility with bentonite, a montomorill-onite clay, has been reported by Danti and Guth306. The incompatibility with lactose, causing a discoloration of the mixture has been studied by Hammouda and Salakawy- 0 . The amount of browning produced was shown to be dependant on the initial pH of the solution. The rate of discoloration of the lactose/neomycin powder was directly related to the temperature of storage and the relative humidity of the atmosphere. Discoloration was overcome by addition of sodium bisulphite. 

The used tablet ingredients were a-lactose monohydrate (Ph.Eur grade, 100 mesh), rice starch (Ph.Eur. grade) and magnesium stearate (Ph.Eur. grade). Before use the magnesium stearate was sieved through a 210 im sieve. Prior to use, the materials were stored at 20 1 °C and 45 5% relative humidity (RH) for at least one week. 

The a-lactose tablets were influenced by the relative humidity too (y5, siR(S) is significant) but the effect was smaller than for the dicalcium phosphate dihydrate tablets. From the tablets investigated, the 6-lactose tablets were least influenced by storage. 

Of the tablets prepared with sodium starch glycolate, only the 6-lactose/sodium starch glycolate combination was influenced by all three adjustable factors (Table 8.8). Moreover, the effect of the relative humidity depended on the level of the temperature as well as the level of the disintegrant concentration and vice versa. 

Figure 8.4 Storage to Initial Ratio of crushing strength (SIR(S)) off-lactose/potato starch tablets, as a function of storage temperature (°C) and storage relative humidity (%RH)...

Each combination behaves differently after storage. In all cases there was an effect of the starch concentration (y i sir(d) is significant). In most cases the relative humidity as well as the interaction between the relative humidity and the disintegrant concentration plays a role in the disintegration time of tablets prepared with either lactose. The dicalcium phosphate dihydrate/rice starch combination is influenced very strongly by the three factors studied. This combination is not suitable for use in tropical countries. Neither is the combination of B-lactose and crospovidone. 

MCC, lactose, calcium phosphate dibasic, and mannitol were selected as common tableting diluents and were evaluated as received from their vendors. These materials are summarized in Table 2. Each material is available from several vendors with multiple grades. Three grades within each excipient were selected for their diverse range of physical and mechanical properties (3). These materials typically comprise 5% to 70% of a formulation. The samples were stored at environmentally controlled laboratory conditions of 20 2°C and 40% 10% relative humidity. 

Note A, stearic acid B, magnesium stearate C, AEROSIL 380 D, lactose E, LUDIPRESS F, corn starch G, AVICEL PH 101 H, methylcellulose I, ethylcellulose J, EUDRAGIT RSPM K, mannitol L, relative humidity M, temperature N-W, pseudo variables. (+) is high level and (-) is low level. 

Kett et al. [1.162] studied Tg in freeze-dried formulations containing sucrose as a function of relative humidity and temperature during storage by TMDSC and ther-mogravimetric analysis. Craig et al. [1.163] found it helpful to asses the relaxation behavior of freeze-dried amorphous lactose by MTDSC. Relaxation times were calculated from measurements of Tg, and the magnitude of the relaxation endotherm. Scannnig was performed at 2°C/min with a modulation amplitude of 0.3 °C and a period of 60 s. 

Fig. 1.69.2. Moisture sorption profiles of anhydrous lactose (1), mannitol (2), trehalose (3) and sucrose (4). Top before and bottom after lyophilization (% weight change from the data in Table 1.10.4) at different relative humidity (RH) changes over 50-60 h. Before lyophilization 1, lactose — 1.1 RH 10%, 1.2 RH 60% 2, mannitol 3, trehalose - 3.1 RH 10%,...

The effects of storage after drying also may be assessed from the equilibrium moisture content curves. Storage conditions are not critical for the lactose granulation.f If the antacid formulation is stored at a relative humidity of only 65% it would, given sufficient time, absorb moisture until the content was 91%. This could be associated with poor flow characteristics and its attendant difficulties during compression. 

Many drugs and excipients (cephalexin monohydrate, quinidine sulfate dihydrate, ampicillin trihydrate, codeine sulfate trihydrate, morphine sulfate dihydrate, dicalcium phosphate trihydrate, raffinose pentahy-drate, lactose monohydrate) utilize water as an integral part of their crystal structure. Solids that form specific crystal hydrates tend to sorb relatively small amounts of water to their external surface below a characteristic relative humidity, when initially dried to an anhydrous... 

Mold growth may occur under humid conditions (80% relative humidity and above). Lactose may develop a brown coloration on storage, the reaction being accelerated by warm, damp conditions see Section 12. The purities of different lactoses can vary and color evaluation may be important, particularly if white tablets are being formulated. The color stabilities of various lactoses also differ. 

Newell HE, et al. The use of inverse phase gas chromatography to study the change of surface energy of amorphous lactose as a function of relative humidity and the processes of collapse and crystallization. Int J Pharm 217(1-2) 45-56, 2001. 

Figure 2 The dynamic vapor sorption chart for lactose. A humidity-induced recrystallization event of spray-dried lactose is marked. Steps refer to relative humidity changes. Source Courtesy of Surface Measurement Systems (1).

Saltmarch, M. and Labuza, T.P. Influence of relative humidity on the physicochemical state of lactose in spray-dried sweet whey powders, /. Food Sci., 45,1231,1980. 

RH relative humidity (%), Gel. St. gelatinized starch, W.C. water content (% dry basis), Nat. St. native starch, T. glass transition temperature (°C), Lact. lactose. 

Samples with lactose as the excipient are usually run at between 0% and 5% relative humidity in the dry box. Single-dose vials containing approximately 5 mg or less per vial are pooled by consecutive delivery into the vessel solution of the contents of four or five vials. 

Figure 12. An RH perfusion device, coupled to an isothermal microcalorimeter was used to study an amorphous to crystalline transformation of a lyophilised drug. The calorimetric signal shows an initial water sorption exotherm as the RH within the perfusion device is changed from 40% RH to 80% RH. There is then a delay followed by recrystallisation of the material. The interval between adsorption and crystallisation is, presumably, related to random nucleation. However there is probably a dependency on hydrophobicity, sample mass, the relative humidity of the chamber and temperature. As a comparison, amorphous P-lactose monohydrate, under the same conditions as above, would take about 30 minutes to recrystallise.

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