Cooh Hc

Figure 1.8 (a) Effect of anionic and cationic surfactants on the habit of adipic acid crystals. (b) A diagrammatic (not to scale) representation of the arrangement of molecules at the crystal surface. Figure 1.8 (a) Effect of anionic and cationic surfactants on the habit of adipic acid crystals. (b) A diagrammatic (not to scale) representation of the arrangement of molecules at the crystal surface. Surfactants in the solvent medium used for crystal growth (or, for example, in stabilisation or...

Info

The release profiles have the pH dependency shown in Fig. 7.24. The release profile follows the expected pH trend, but a more detailed analysis shows that the majority of the drug is associated with the phospholipid. Most emulsions, unless very dilute, display both plastic and pseudoplastic flow behaviour rather than simple Newtonian flow. The flow properties of fluid emulsions should have little influence on their biological behaviour, although the rheological characteristics of semisolid...

Activity of ionised drugs

A large proportion of the drugs that are administered in aqueous solution are salts which, on dissociation, behave as electrolytes. Simple salts such as ephedrine hydrochloride (C6H5CH(OH)CH(NHCH3)CH3HCl) are 1 1 (or uni-univalent) electrolytes that is, on dissociation each mole yields one cation, C6H5CH(OH)CH(N +H2CH3)CH3, and one anion, Cl0. Other salts are more complex in their ionisation behaviour for example, ephedrine sulfate is a 1 2 electrolyte, each mole giving two moles of the cation...

Ionisation of polyprotic drugs

In the examples we have considered so far, the acidic drugs have donated a single proton. There are several acids, for example citric, phosphoric and tartaric acids, that are capable of donating more than one proton these compounds are referred to as polyprotic or polybasic acids. Similarly, a polyprotic base is one capable of accepting two or more protons. Many examples of both types of polyprotic drugs can be found in Table 3.6, including the polybasic acids amoxicillin and fluorourocil, and...

Solubility problems in formulation Shtore XV Sulfamethoxazole pKa 603

Solution sulfamethoxazole and trimethoprim demonstrate a high degree of incompatibility and mutual precipitation occurs on mixing. To optimise mutual dissolution, an aqueous solution which includes 40 propylene glycol is utilised in the formulation of the infusion. This solution, which has a pH between 9.5 and 11.0, allows adequate amounts of both substances to coexist in solution to give the correct ratio of concentration for antibacterial action. On dilution, the infusion becomes less 5.7.1...

Osmotic properties of drug solutions

A nonvolatile solute added to a solvent affects not only the magnitude of the vapour pressure above the solvent but also the freezing point and the boiling point to an extent that is proportional to the relative number of solute molecules present, rather than to the weight concentration of the solute. Properties that are dependent on the number of molecules in solution in this way are referred to as colligative properties, and the most important of such properties from a pharmaceutical...

Puw

Figure 12.4 A recommended standard design for a flow-through cell the cell is cylindrical in shape and constructed of glass or other suitable material. A, an internal volume not exceeding 20 cm3 between barrier and filter. B, a bottom barrier of either a porous glass plate or a bed of 1 mm diameter glass beads designed to disperse flow and provide uniform distribution over the dosage chamber A. C, a suitable filter of approximately 25 mm diameter. D, fluid flow from bottom to top.

Drugs Partitioning Between Aqueous Phases And Lipid Biophases

They are virtually unabsorbed from the gut and indeed are used in the treatment of worm infestation of the lower bowel. plastic containers into formulations. It is, therefore, important that the process can be quantified and understood. Here we discuss the topic of partitioning of a drug or solute between two immiscible phases. One phase might be blood or water and the other a biomembrane, or an oil or a plastic. As many processes (not least the absorption process)...

C C N H Ch3

Figure 10.4 (a) A highly simplified diagram of a kidney tubule to illustrate the filtration and secretion of drugs from the blood into the tubular filtrate, and their subsequent reabsorption or loss in the urine. (b) Schematic representation of the influence of urinary pH on the passive reabsorption of a weak acid and a weak base from the urine in the renal tubules at a high pH the passive reabsorption of the weak base and the excretion of the weak acid are enhanced, while at a low pH values...

Preparation Of Microcapsules By Temperature Change Method

Table 8.12 Depot forms employing polymeric films and matrices Diagrammatic representation Mechanisms Beeswax, glyceryl monostearate, ethylcellulose, nylon (Ultramid IC), acrylic resins (Eudragit retard) Glycerol palmitostearate (Precirol), beeswax, glycowax, castorwax, aluminium monostearate, carnauba wax, glyceryl monostearate, stearyl alcohol Polyethylene Poly(vinyl acetate) Polymethacrylate Poly(vinyl chloride) Ethylcellulose 6 Hydrophilic matrix Carboxymethylcellulose Sodium...

Preparation of isotonic solution

Since osmotic pressure is not a readily measurable quantity, it is usual to make use of the relationship between the colligative properties and to calculate the osmotic pressure from a more easily measured property such as the freezing point depression. In so doing, however, it is important to realise that the red blood cell membrane is not a perfect semipermeable membrane and allows through small molecules such as urea and ammonium chloride. Therefore, although the quantity of each substance...

The chemical decomposition of drugs

In this section we examine various ways in which drugs in both liquid and solid formulations can lose their activity, so that we can be aware of those chemical groups which, when present in drug molecules, can cause stability problems. We will later see how to prevent or minimise the chemical breakdown for each type of decomposition process. Although each decomposition scheme is considered separately, it should be noted that with some drug molecules more than one type of decomposition may be...

The solubility of anaesthetic gases in blood and tissues

Blood solubility and anaesthetic action Anaesthetic gases such as ether which have a high blood solubility (Ostwald solubility coefficient in blood is 12) are transported away from the lungs more rapidly than those such as halothane (Ostwald coefficient 2.3) and nitrous oxide (Ostwald coefficient 0.47). As a consequence, the concentration of ether in alveolar air builds up more slowly than that of the more poorly soluble anaesthetic gases and is only slightly above the level in the tissues....

Ph

Figure 6.19 pH profile for the sorption of benzocaine by nylon 6 powder from buffered solutions at 30 C and ionic strength 0.5 mol dm03 (O) and the corresponding drug dissociation curve ( ). Reproduced from N. E. Richards and B. J. Meakin, J. Pharm. Pharmacol., 26, 166 (1974) with permission. Of the two effects, the solubility effect is usually the stronger. Thus, in the adsorption of hyoscine and atropine on magnesium tri-silicate it was noted5 that hyoscine, although in its completely...

T

A G1 is therefore zero at the theta temperature when deviations from ideality vanish, that is, there are no polymer-polymer or polymersolvent interactions. When T 0 there can thus be no stabilisation as molecules will interpenetrate without net interaction and will exert no forces on each other. Not only do most linear polysaccharides tend to form spirals in solution, but in their tendency to associate they may form double helices, as does carrageenan, for instance. Under certain conditions of...

B

EXAMPLE 4.5 Calculation of the catalytic coefficients for buffer species The following data were obtained for the hydrolytic rate constant k of codeine sulfate at 100 C in phosphate buffers of varying total concentration BT at pH values of 6 and 8 BT(moldm-3) 0.03 0.06 0.09 0.12 107k (s01) at pH 6 6.1 11.2 16.3 21.4 107k (s01) at pH 8 12.9 25.0 37.0 49.0 If the fraction of H2PO- present in buffer solutions at pH 6 is 0.74 and at pH 8 is 0.23, determine graphically the catalytic coefficients for...

Oh

Figure 4.2 First-order plot for hydrolysis of homatropine in hydrochloric acid (0.226 mol dm-3) at 90 C. Data from M. H. Krasowska, S. Schytt Larsen and K. Ilver, Dansk. Tidsskr. Farm., 42, 170 (1968) with permission. The rate of a second-order reaction is determined by the concentrations of two reacting species. The general rate equation is given by equation (4.3) as

Summary

The most common cause of degradation of drugs in aqueous systems is hydrolysis and the most susceptible drugs are those containing ester, amide, lactone, lactam, imide or carbamate groups. Hydrolysis can be controlled by adjusting the pH to that of maximum stability or in some cases by the addition of nonaqueous solvents. Oxidative degradation is a problem with drugs possessing carbon-carbon double bonds such as the steroids, polyunsaturated fatty acids and polyene antibiotics. Such drugs can...

Answer

Codeine is a weakly basic drug and hence its pH will be given by where c 1 g in 120 cm3 8.33 g dm 3 0.02633 mol dm 3. Because of the limited solubility of many weak acids and weak bases in water, drugs of these types are commonly used as their salts for example, sodium salicylate is the salt of a weak acid (salicylic acid) and a strong base (sodium hydroxide). The pH of a solution of this type of salt is given by Alternatively, a salt may be formed between a weak base and a strong acid for...

Surfactants

6.1 Amphipathic compounds 178 6.5 Properties of some commonly used 6.2 Surface and interfacial properties of surfactants 216 surfactants 179 6.6 Solubilisation 220 6.3 Micellisation 201 Summary 227 6.4 Liquid crystals and surfactant References 228 vesicles 210 Certain compounds, because of their chemical structure, have a tendency to accumulate at the boundary between two phases. Such compounds are termed amphiphiles, surface-active agents, or surfactants. The adsorption at the various...

Physicochemical drug interactions and incompatibilities

10.1 pH effects in vitro and in vivo 395 10.7 Adsorption of drugs 414 10.2 Dilution of mixed solvent systems 401 10.8 Drug interactions with plastics 417 10.3 Cation-anion interactions 402 10.9 Protein binding 419 10.4 Polyions and drug solutions 405 Summary 425 10.5 Chelation and other forms of Appendix 425 complexation 405 References 429 10.6 Other complexes 410 Further reading 430 This chapter deals with some practical consequences of the physical chemistry of drugs -particularly their...

Hydrolysis

Drugs susceptible to hydrolytic degradation How can we tell whether a drug is likely to be susceptible to this type of degradation If the drug is a derivative of carboxylic acid or contains functional groups based on this moiety, for example an ester, amide, lactone, lactam, imide or carbamate (see Scheme 4.1), then we are dealing with a drug which is liable to undergo hydrolytic degradation. We will consider some examples. Drugs that contain ester linkages include acetylsalicylic acid...

M

Substituting for vh in equation (8.10), V limc J v(V2 + d,vf) chapter in discussion of individual macro-molecules, for example, gum Arabic (acacia). The viscosity of solutions of globular proteins (which are more or less rigid) is only slightly affected by change in ionic strength. The intrinsic viscosity of serum albumin varies only between 3.6 and 4.1 cm3 g 1 when the pH is varied between 4.3 and 10.5 and the ionic strength between zero and 0.50. Viscosity in pharmacopoeial specifications In...

H

Figure 6.22 Diagram angle and length. electrons. This pairing leaves two lone pairs of electrons in the outer-shell, the orbitals of which point to the vertices of an approximately regular tetrahedron formed by the lone pairs and the OH bonds. The resulting tetra-hedral structure has two positively charged sites at one side and two negatively charged sites at the other. It will readily attach itself by hydrogen bonds to four neighbouring molecules, two at the negatively charged sites and two at...

T0r

Mole fraction may be replaced by molality, m, using the relationship where Kb is the molal elevation constant, which has the value 0.511 K mol-1 kg for water, and My is the molecular weight of the solvent. point lowering can be derived in a similar manner to that for boiling point elevation, giving where AHfus is the molal heat of fusion. Therefore, where Kf is the molal freezing point constant, which is 1.86 K mol 1 kg for water. The amount of gas which can be dissolved by a particular liquid...

Microdissociation constants

The experimentally determined dissociation constants for the various stages of dissociation of polyprotic and zwitterionic drugs are referred to as macroscopic values. However, it is not always easy to assign macroscopic dissociation constants to the ionisation of specific groups of the molecule, particularly when the pKa values are close together, as discussed in section 3.5.4. The diprotic drug morphine has macroscopic pKa values of 8.3 and 9.5, arising from ionisation of amino and phenolic...

Ch2oh

Hydroxyl groups cannot bond onto the water 'lattice' without causing it to distort considerably. This may be one explanation of the difference, although differences in the lattice energies of the crystals may also contribute. Hydration of ionic species water structure breakers and structure makers The study of ionic solvation is complicated but is relevant in pharmaceutics because of the effect ions have on the solubility of other species. The forces between cations and water molecules are so...

Bpcs Of Neomycin

In fine powderb form for preparation of Soluble Aspirin Tablets and Soluble Aspirin, Phenacetin and Codeine Tablets Surface area of not less than 7000 cm2 g01 determined by air permeability method Ultrafine powder to be used for preparation of solid dosage forms to achieve a satisfactory rate of solution Colloidal water-miscible type differentiated from nondispersible form by size Fine powder to be used for preparation of solid dosage forms Prepared from dithranol in fine powder form Most of...

P50

See also containers glass plastics palmitic acid 187 pan coating 317 paracetamol bioavailability 387 polymorphism 14-15, 17 transacetylation with aspirin 125 parallel reactions 108-9 parenteral fluids, pH 153, 154 partial molar quantities 67 particle size and deposition in alveoli 380, 380-1 and solubility 24 biopharmaceutical importance 23-6 control in compendia 25 distribution in aerosols 378, 475-7 effect on drug release 470 measurement in aerosols 475-7 particles diameter 378 gravitational...

C6h5och2cooh

Figure 5.15 Diagram showing opportunities in plastic systems for adsorption of drug molecules, partitioning into and eventually permeation through the plastic. Leaching of molecules from the plastic also may occur. 5.10.3 A chromatographic model for the biophase Octanol water partition coefficients, as we have seen, have been useful predictors of biological activity. In spite of this it has been suggested that bulk liquid phases may not be the most appropriate models for a structured biophase...

Hob

Complexation, precipitation or phase separation can occur in these circumstances, the product being affected by changes in ionic strength, temperature and pH. Examples of cation-anion interactions include those between procainamide and phenytoin sodium, procaine and thiopental sodium, and hydroxyzine hydrochloride and benxylpeni-cillin Scheme 10.1 . The nature of many of these interactions has not been studied in detail. In the absence of such work it is necessary to predict possible...

Hlb

Figure 7.13 Variation of mean globule size in a mineral oil-in-water emulsion as a function of the HLB of the surfactant mixtures present at a level of 2.5 . Surfactants Brij 92-Brij 96 mixtures. Source P. Depraetre, M. Seiller, A. T. Florence and F. Puisieux unpublished . nonionic surfactants, an optimal HLB of between 7.5 and 8 is identified. At the optimum HLB the mean particle size of the emulsion is at a minimum Fig. 7.13 and this factor would explain to a large extent the stability of the...

Ordinary ampholytes

In this category of ampholytes, the pKa of the acidic group, pKfidic, is higher than that of the basic group, pKbasic, and consequently the first group that loses its proton as the pH is increased is the basic group. Table 3.6 includes several examples of this type of ampholyte. We will consider, as a simple example, the ionisation of m-aminophenol I , which has pKfidic 9.8 and pKbasic 4.4. The steps of the ionisation on increasing pH are shown in the following equilibria

Pvp 11500

Figure 8.21 The influence of PVP 11 500 and PVP 40 000 on the aqueous solubility of testosterone at 37 C. Reproduced from A. Hoelgaard and N. Muller, Arch. Pharm. Chem., 3, 34 1975 . molecular weight the comparable value for Macrogol 1540 is only 30 . They are used as solvents for drugs such as hydrocortisone. The macrogols are incompatible with phenols and can reduce the antimicrobial activity of other preservatives. Higher molecular weight PEGs HO CH2CH2O H Structure XV Polyoxyethylene glycol...