Microcrystalline formulations

Intramuscular Route. The IM route is frequently used for drugs dissolved in oily vehicles or for those in a microcrystalline formulation that are poorly soluble in water (e.g., procaine or penicillin G). Advantages include rapid absorption (often in under 30 min), the opportunity to inject a relatively large amount of solution, and a reduction in pain and local irritation compared with SC injections. Potential comphcations include infections and nerve damage. The latter usually results from the choice of an incorrect site for injection. 

The incidence of gastrointestinal side-effects including nausea, vomiting and diarrhoea with nitrofurantoin is as high as 30% with standard microcrystalline formulations and patients should be advised to take the doses with food. Other important but less common adverse reactions include pulmonary fibrosis, peripheral neuropathy and hypersensitivity. Patients should also be warned that nitrofurantoin can colour the urine yellow or brown. 

The lambda type is nongelling, and functions as a thickner. Iota-carrageenan has been recommended (45) for use in formulating low fat ground beef due to its abihty to retain moisture, especially through a freeze—thaw cycle which is typical for ground beef patties. Oat bran and oat fiber can also be used to improve moisture retention and mouth feel. Modified starches can be used as binders to maintain juiciness and tenderness in low fat meat products. Maltodextrins (dextrose equivalent less than 20) may be used as binders up to 3.5% in finished meat products. Other carbohydrates such as konjac flour, alginate, microcrystalline cellulose, methylceUulose, and carboxymethylceUulose have also been used in low fat meat products (see CELLULOSE ETHERs). 

The exact formulations for inlay casting waxes are considered trade secrets, and Htfle has been pubUshed on the subject. A binary mixture of 65—75 wt % paraffin wax (60—63°C) and a microcrystalline wax having a melting point >60° C has been suggested (127). This produces a mixture having a sohd—sohd transition point at about 37°C with htfle plastic deformation (1—3%) at 37°C and a desirable plasticity at 45°C (73—77%) (128). 

Base-plate wax compositions are generally regarded as trade secrets. A substantial percentage of paraffin is usually present, probably 50—80 wt %. Beeswax [8012-89-3] camauba wax [8015-86-9] ceresin, microcrystalline waxes, Acrawax C (Glyco Products Co. Inc.), mastic gum, rosin [8050-09-7] and synthetic resins may make up the balance of the formulation. Base-plate waxes are generally sold in sheet form about 1.3 mm thick, 75 mm wide, and 140 mm long. 

Some tablets combine sustained-release and rapid disintegration characteristics. Products such as K-Dur (Key Pharmaceuticals) combine coated potassium chloride crystals in a rapidly releasing tablet. In this particular instance, the crystals are coated with ethylcellulose, a water-insoluble polymer, and are then incorporated into a rapidly disintegrating microcrystalline cellulose (MCC) matrix. The purpose of this tablet is to minimize GI ulceration, commonly encountered by patients treated with potassium chloride. This simple but elegant formulation is an example of a solid dosage form strategy used to achieve clinical goals. 

Fig. 12 Percent weight gain associated with the exposure of tablet formulations to 80% relative humidity at 40°C. Formulation A (0) was essentially a 1 11 blend of the drug entity and microcrystalline cellulose, while formulation B ( ) was essentially 1 5.5 5.5 drug-microcrystalline cellulose-starch.

Formuiation The formulation consists of excipients such as carnauba wax, crospovidone, hydroxylpropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, and other inactive ingredients. 

Spherical pellets containing 5% triamcinolone acetonide were prepared by Villar-Lopez and co-workers [59] by extrusion/spheronization following formulation with microcrystalline cellulose and/or a hydrophilic excipient like lactose, sodium earbox-ymethylcellulose, or P-cyclodextrin. Their suitability for coating, with a view toward colonic drug deliveiy, was assessed in terms of their size, sphericity, and dissolution test response. The best results were afforded by a 5 90 5 composition of microcrystalline cellulose, P-cyclodextrin, and triamcinolone acetonide, prepared by complex-ation of triamcinolone acetonide with P-cyclodextrin prior to the addition of microcrystalline cellulose. 

The analogous reaction of 3 with W2(OrBu)6 gave a brown solution, from which a yellow, microcrystalline material could be isolated. Based on spectroscopic data the latter was formulated as [Cy7Si70i2]2W2(p-H)(0tBu) (158). Cleavage of the Mo = Mo triple bond in 157 occurred upon treatment of this compound with NO (two equivalents) to afford the dimeric nitrosyl molybdenum silsesquioxane complex [Cy7Si70i2]2Mo2(NO)2 (159). °°... 

Formulation Silicon Polypropylene (major binder) Microcrystalline wax (minor binder) Stearic acid... 

Using silicon nitride powder in a polypropylene/microcrystalline wax/stearic acid binder formulation, the effect of filler volume fraction (V) (over the range 50 to 70%) on relative viscosity (rjj.) was predicted from Eq. 5 ... 

The study was then extended to monitor the scale-up of a pharmaceutical blend containing an active pharmaceutical ingredient. A binary mixture of acetaminophen (APAP) with microcrystalline cellulose was selected as the model formulation. The ability of NIR spectroscopy to monitor real-time content uniformity in addition to the aforementioned compact attributes, during roller compaction was also tested. 

Harrison et al. (27,31) obtained force-displacement profile during extrusion of microcrystalline cellulose (MCC) only formulations using a ram extruder and resolved it into three stages, as seen in Figure 9 compression, steady state, and forced flow. Based on surface smoothness and cohesive strength, a predominant steady state region was found necessary... 

Guo M, Augsburger LL. Potential application of silicified microcrystalline cellulose in direct-fill formulations for automatic capsule-filling machines. Pharm Dev Technol 2003 8(l) 47-59. 

Improvements in theophylline preparations have come from alterations in the physical state of the drugs rather than from new chemical formulations. For example, the increased surface area of anhydrous theophylline in a microcrystalline form facilitates solubilization for complete and rapid absorption after oral administration. Numerous sustained-release preparations (see Preparations Available) are available and can produce therapeutic blood levels for 12 hours or more. These preparations offer the advantages of less frequent drug administration, less fluctuation of theophylline blood levels, and, in many cases, more effective treatment of nocturnal bronchospasm. 

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

Strain rate sensitivity of (or the effect of press speed on) the formulation is of primary concern in scale-up. Whether the product development work was performed on a single-stroke press or a smaller rotary press, the objective in operations will be to increase efficiency, in this case the tablet output rate and, therefore, the speed of the press. For a material that deforms exclusively by brittle fracture, there will be no concern. Materials that exhibit plastic deformation, which is a kinetic phenomenon, do exhibit strain rate sensitivity, and the effect of press speed will be significant. One must be aware that although specific ingredients (such as calcium phosphate and lactose) may exhibit predominately brittle fracture behavior, almost everything has some plastic deformation component, and for some materials (such as microcrystalline cellulose) plastic deformation is the predominant behavior. The usual parameter indication is that target tablet hardness cannot be achieved at the faster press speed. Slowing the press may be the only option to correct the problem. 

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