Effect of ultraviolet light on the release of theophylline from ethylcellulose-based sustained-release microcapsules.

Sustained-release theophylline microcapsules were prepared using the emulsion solvent-evaporation technique. Three viscosity grades of ethylcellulose and varying concentrations of theophylline were used for the formulation. The microcapsules were exposed to short-wave ultraviolet (UV) light for 7 days. The surface and the cross-section of microcapsules were analyzed by scanning electron microscopy (SEM). The release of drug was determined by using the USP dissolution apparatus. Differential scanning calorimetry (DSC) was used to study the thermal properties of theophylline and the polymer. SEM revealed numerous pores on the surface of microcapsules. The size of the pores increased on exposure to light. Theophylline release from microcapsules was found to follow first-order kinetics both before and after UV light exposure. The drug release rate from microcapsules exposed to short-wave UV light increased by about 80%-450% compared with the unexposed samples. The release of theophylline from the microcapsules was more faster with higher concentration of ethylcellulose polymer. Both SEM and DSC showed uniform dispersion of drug with the polymer within the microcapsules. The melting point of the polymers changed, but it remained unchanged for theophylline on exposure to UV light. The UV light caused photodegradation or depolymerization of the polymer and thus caused a faster release of drug from the sustained-release microcapsules. The finding underscores the need for setting standards and requirements for light-stability testing for sustained-release formulations, where there may be substantial change in the release pattern of drug on exposure to light.

Photodegradation of furosemide solutions.

Photodegradation of furosemide was studied under the influence of fluorescent and UV lights. Photodecomposition of furosemide solutions appeared to follow first-order kinetics. The compound was found to be most stable at an optimum pH of 7. Long-wave UV light caused the fastest rate of degradation of furosemide. Glutathione, thiourea, EDTA, sodium thiosulfate, sodium metabisulfite, glycine, sodium benzoate and uric acid were found to be ineffective as photoprotective agents. Increase in ionic strength did not cause any change in the degradation rate constant. Amber glass vials and transparent glass vials covered with aluminum foil offered complete protection against fluorescent light. A vehicle consisting of a mixture of 50% (v/v) propylene glycol in phosphate buffer offered slight photoprotection.

Photostability profiles of minoxidil solutions.

Photostability profiles of minoxidil solutions exposed to fluorescent light, under the influence of several parameters like concentration, pH, buffer species, photostabilizers, container type, solvent system, and skin penetration enhancers were studied. The assay of minoxidil was done spectrophotometrically at 230 nm and 290 nm, using double beam UV-visible spectrophotometer. The results show that photodegradation of minoxidil solutions follows first order rate. Furthermore, minoxidil solution (4.5 micrograms/ml) was found to be more stable in phosphate buffer as compared to acetate buffer. Amber glass offered equivalent photoprotection as aluminum foil-covered glass. Minoxidil was found to be most stable in a solvent system of water or 25% v/v PEG300 and least stable in 25% v/v propylene glycol. Of the penetration enhancers studied dimethyl sulfoxide (DMSO) caused the least photodecomposition of minoxidil. The order of photoprotection of the five potential photostabilizers were as follows: sodium thiosulfate > EDTA > sodium benzoate approximately thiourea > sodium metabisulfite. Varying the concentration of sodium thiosulfate did not affect the minoxidil photostability. The study also indicates that minoxidil solution (4.5 micrograms/ml) is most photostable in pH 8 phosphate buffer. An increase in ionic strength had a photostabilizing effect until an optimum strength of 0.17, then further increase caused the rate of photodegradation to remain unchanged.

Photoprotection of daunorubicin hydrochloride with sodium sulfite.

Protection of 10(-4) M daunorubicin hydrochloride (DNRUB) solutions against photolytic degradation was investigated using sodium sulfite (SS). Photodegradation of the drug under fluorescent light was found to be accelerated at higher pHs, and the photoprotecting ability of SS (1.9 x 10(-3) M) increased progressively with an increase in pH in the range of 3.7 to 8.2. Increase in ionic strength (mu) appeared to decrease the rate of degradation of the drug, in the presence or absence of SS, in acetate buffer (0.1 M) of pH 5.5. Photostability of DNRUB solutions was enhanced with an increase in SS concentration in pH 6.5 citrate buffer (0.1 M, mu = 0.5). The effect of various buffer species on the photostability of DNRUB was carried out using acetate, phosphate and citrate buffers. Divalent phosphate anion appeared to demonstrate the greatest catalyzing effect followed by trivalent citrate, combination of divalent and trivalent citrate (9:11 molar ratio), and monovalent acetate anion. Sodium sulfite was found to significantly diminish the catalyzing effect of all the buffers.

Effect of sodium thiosulfate on the photolysis of phenobarbital: evidence of complex formation.

Photodegradation of phenobarbital in aqueous solutions exposed to short-wave ultraviolet light was studied in presence and in absence of sodium thiosulfate. The degradation process appeared to follow first-order kinetics and was found to be dependent on pH, buffer system and sodium thiosulfate concentration. Ionic strength did not have any appreciable effect. The rate of photodegradation was found to be inversely proportional to phenobarbital concentration, especially below 8 x 10(-4) M. Solutions of phenobarbital containing alcohol, propylene glycol and benzyl alcohol as cosolvents showed markedly improved stability under UV irradiation in absence of sodium thiosulfate. Complex formation between the thiosulfate anion and phenobarbital appeared to be primarily responsible for the photostabilization of the drug. The equilibrium constant for this complex was calculated to be 36.23 M-1.

Photostabilization of dacarbazine with reduced glutathione.

Reduced glutathione was found to guard against photodecomposition (under fluorescent light) of the anticancer drug dacarbazine (DTIC). Increase in pH appeared to accelerate the degradation of DTIC within a pH range of 4.5-8.1. The stabilizing effect of reduced glutathione was found to increase with its concentration reaching an optimum value at 5 mg%. Increase of ionic strength slightly enhanced the photostability of DTIC solutions in pH 7 phosphate buffer (0.05 M). Different buffer systems at pH 4.5 did not significantly alter the degradation rate of the drug in the absence of reduced glutathione. However, in presence of reduced glutathione, dacarbazine appeared to be less stable in acetate buffer of pH 4.5.

Photostabilization of riboflavin by incorporation into liposomes.

The influence of liposomes on the photostabilization of riboflavin in an aqueous formulation was studied under fluorescent light at various conditions. Liposomal composition, concentration, pH, and ionic strength were varied. The photostability of riboflavin was found to increase in the presence of neutral and negatively-charged liposomes but to decrease in association with positively-charged liposomes. Furthermore, increasing the concentration of dimyristoyl-phosphatidylcholine (DMPC) in the composition of the liposomes resulted in an enhancement in the photostability of riboflavin such that at 5.8mM DMPC concentration a 2.3 fold increase in photostability was observed compared to control buffer solution. The pH of the medium influenced the photostability of riboflavin. However, the ionic strength of solution appeared to demonstrate no significant effect. The photodegradation reactions appeared to follow first-order kinetics in the presence and absence of liposomes.

Effect of certain additives on photodegradation of tetracycline hydrochloride solutions.

The photostability of tetracycline hydrochloride solutions in the presence of selected potential stabilizers under various light sources was investigated. Reduced glutathione (GSH) demonstrated the greatest photostabilizing effect followed by p-aminobenzoic acid (PABA), ethylenediamine tetraacetic acid (EDTA) disodium salt, DL-cysteine, thiourea, sodium thiosulfate, and DL-methionine in a descending order. The photostabilizing effect of GSH was found to be dependent on its concentration, pH and buffer species of the medium, the light source, and the temperature of the solutions exposed to light.

Photostabilization of doxorubicin hydrochloride with radioprotective and photoprotective agents: potential mechanism for enhancing chemotherapy during radiotherapy.

p-Aminobenzoic acid (PABA), urocanic acid, and sodium urate were found to significantly enhance the photostability of doxorubicin hydrochloride [adriamycin, (ADR)]. d1-Methionine, thiourea, and glycine also increased the photostability of this drug, but to a lesser degree. Sodium thiosulfate on the other hand, was found to be detrimental to the photostability of ADR. The photostabilizing effect of PABA was found to increase with increase of its concentration and was influenced by the pH and the buffer species of the vehicle. The findings would have an impact on the enhancement of therapeutic efficacy of adriamycin when administered during radiation therapy.

Photostabilization of menadione sodium bisulfite by glutathione.

Photodecomposition of solutions of menadione sodium bisulfite (MSB) in the presence and absence of glutathione (GSH) under artificial sunlight was investigated. In presence of 0.02% (GSH), an appreciable increase in photostability was observed when clear glass vials were used. The pH and the temperature of the solution significantly influenced the stability of MSB. Photodegradation of MSB appeared to follow first-order kinetics. Photostabilization of MSB was attributed in part to complex formation between MSB and GSH and the antioxidant property of the latter. Stability constants for the various solutions were determined at several temperatures. Thermodynamic parameters were calculated and were found to support complex formation.

Complex formation between metronidazole and sodium urate: effect on photodegradation of metronidazole.

Photodegradation of solutions of metronidazole in the presence and absence of sodium urate was studied. Photodegradation appeared to follow zero-order kinetics and was found to be dependent on the pH, buffer species, sodium urate concentration, and light source. Complex formation between metronidazole and sodium urate accounted for the photostabilization of metronidazole. The dissociation constant for this complex was calculated to be 3.4 x 10(-3) M.

Effect of dimethylpolysiloxane fluid on the stability and dissolution of prednisolone.

The physicochemical effects of a dimethylpolysiloxane fluid as a vehicle for prednisolone on its stability and dissolution pattern were evaluated. No detectable degradation of prednisolone was noted during 8 weeks of storage at 4, 26 and 45 degressC. The release rate of prednisolone from its suspension in dimethylpolysiloxane was lower than that from the aqueous suspension. However, the amount of prednisolone released in 30 min from the aqueous suspension was only about 5.5% greater than that released from its suspension in the silicone fluid.

Interaction of salicylic acid with adenosine and adenosine triphosphate. Potential mechanism of intensifying acetylsalicylic acid-induced GI blood loss.

Complex formation between salicylic acid and adenosine or adenosine triphosphate in 0.2m phosphate buffer at pH=7 was investigated as a potential factor contributing to the prolongation of acetylsalicylic acid-induced GI blood loss. Spectrophotemetric techniques were used to evalute the complexation. Concerntration dependency of the absorbance decrease was measured at 27 and 37 degrees C. The addition of salicylic acid to either adenosine or adenosine triphosplate solutions appeared also to cause a decrease in surface tension which may play a role in reducing platelet aggregation induced by adenosine diphosphate. The results obtained seem to support the opinion that the mechansim of acetylsalicylic acid-induced GI blood loss is due to a combination of both local and systemic effect.

Stability of aspirin in liquid and semisolid bases V: polyglycerol esters.

The stability of aspirin in decaglycerol tetraoleate, decaglycerol octaoleate, and decaglycerol decaoleate was studied at 4, 26, and 45 degrees. Degradation of aspirin in these polyglycerol esters was temperature dependent. Aspirin demonstrated the greatest stability in decaglycerol octaoleate and the lowest stability in decaglycerol tetraoleate at all temperatures studied. The hydroxyl value and the viscosity of the polyglycerol ester appeared to influence the stability of aspirin.

Dissolution of acetylsalicylic acid from acetylsalicylic acid-polyethylene glycol 6000 coprecipitates.

Investigation of possible enhancement of dissolution of acetylsalicylic acid via coprecipitation with polyethylene glycol 6000 was carried out. The results indicated that the initial amount of acetylsalicylic acid released from its coprecipitates or physical mixtures with polyethylene glycol 6000 was increased over that amount released from plain acetylsalicylic acid powder during the same period of time. This was attributed to lowering of the surface tension of the dissolution medium imparted by polyethylene glycol 6000. The effect of particle size of the coprecipitate on the dissolution rate of acetylsalicylic acid was also studied. Greater viscosity values produced by higher concentrations of polyethylene glycol 6000 in the coprecipitates appeared also to influence the dissolution rate of acetylsalicylic acid. The use of optimum concentration of polyethylene glycol 6000 in physical mixtures or coprecipitates would seem advantageous in the preparation of solid dosage forms containing acetylsalicylic acid.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 6: Effect of drug.

The effect of addition of ascorbic acid, which is a drug known to be difficult to compress directly, on the self-binding efficiency of tragacanth, Carbowax 4000, Plasdone, and mannitol were investigated. The flow properties of ascorbic acid of different particle sizes were determined since they would affect the flowability of the binders investigated and would help to determine the optimum particle size of the drug required for maximum binding efficiency.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 7: Formulation and evaluation of ascorbic acid and phenobarbitone tablets.

Directly compressible powder blends containing either ascorbic acid or phenobarbitone, and utilizing tragacanth, Carbowax 4000, Plasdone, and mannitol as dry binders, were formulated. The flowability of the powder mixes prior to compression was determined. Furthermore, the tablets prepared according to the suggested formulae were tested for hardness, friability, uniformity of weight, distribution of active ingredient, disintegration, and dissolution. The effect of aging on the qualities of the tablets was also studied.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 5: Effects of lubricants and flow conditions.

The effect of talc, magnesium stearate, stearic acid, and Acrawax C, which are commonly used as lubricants, on the dry-binding efficiency of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone, and mannitol were investigated. The effect of Aerosil which is sometimes utilized as a flow conditioner for directly compressible powder blends was also studied. The type and concentration of lubricant or flow conditioner appeared to influence the binding efficiency of the binders investigated to various degrees. The results showed that the bonding characteristics of all the binders tested except mannitol were reduced by the addition of the lubricants and the flow conditioner.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 3: Effect of diluents.

The effects of lactose and dibasic calcium phosphate as diluents on the dry-binding qualities of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone and mannitol were investigated. The type, concentration and particle size of the diluent appeared to influence the flowability and the binding properties of the binders investigated.