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A spectrophotometric assay for determining tolmetin sodium in pharmaceutical solid dosage forms is described. Tolmetin sodium is separated from common pharmaceutical excipients and probable degradation products. Recovery, precision, and accuracy data are provided. Two TLC methods are included which can be used to monitor qualitatively the stability of aged dosage forms.
Two kinds of dosage forms of commercially available suppositories containing ketoprofen (KP), fatty suppositories (FS) and gelatin capsulated suppositories (GCS), were administered to patients immediately after anal surgery, and results obtained were compared. No difference was found in each corresponding pharmacokinetic parameter of the two dosage forms. However, when these parameters were compared with those from healthy subjects, significant differences were found in the values of peak level (Cmax), peak time (Tmax) and terminal phase half-life (t1/2). Cmax decreased by one half, and Tmax and t1/2 increased two and four times longer, respectively, those from healthy subjects. The absorption rate constant (ka) in patients was significantly (p less than 0.01) smaller than that in healthy subjects. However, the distribution volume/bioavailability (Vd/F), elimination rate constant (kel), and area under the curve (AUC) differed only slightly. Consequently, the flip-flop phenomena could be seen in the time profiles of plasma KP concentration of patients. These results suggested that the rectal suppository of KP should be administered with care, especially in the patients operated on under spinal anesthesia.
A colorimetric procedure for benzocaine and a number of its dosage forms was developed; it offers improvement in ease, speed, and sensitivity over the official method. The method is based on the formation of a red Schiff base between benzocaine and p-dimethylaminocinnamaldehyde in a nonaqueous acidic medium. At the maximum absorption of 544 nm, the Beer-Lambert law was adhered to over the 0.025--2.5-microgram/ml range. Best accuracy can be obtained for solutions containing 0.25--1.25 microgram/ml. The color was stable for at least 2 hr. Analysis of benzocaine in the dosage forms studied can be directly performed without prior drug extraction.
Capillary isotachophoresis was employed to determine dimethindene in various dosage forms. Several electrolyte systems of varying compositions and varying pH were tested. For validation of the method and the determination of dimethindene in real samples (gel, drops, capsules), two electrolyte systems were selected. Precision, correctness, linearity, robustness, and selectivity of the ITP method were evaluated for both electrolyte systems. The pre-treatment of the sample prior to analysis consisted in dissolving and diluting the pertinent dosage form containing dimethindene with demineralized water to the required concentration. The sample adjusted in this way was directly dosed into the apparatus.
OBJECTIVE: To study pharmacological action variety of ZhongSheng Pill dosage form changing from pill to capsule. METHODS: Using anti-pathogenic microbe, antipyretic and antipyrotic effect as the pharmacological index,we compared the pharmacological action between Zhongsheng Pill formation and Capsule formation. RESULTS: Zhongsheng Capsule had various degrees extraneous antagonistic actions against familiar and conditioned pathogenic bacteria and virus of respiratory tract. Furthermore it coud also reduce the death ratio of mouse infected by staphylococcus aureus and influenza virus, remove fever and diminish inflammation. All these effects had the dose-effect relationship. There were no difference between pill fromation and cpasule formation. CONCLUSION: Zhongsheng Capsule retain the original pharmacological action of Zhongsheng Pill after dosage form changing.
There is much interest in predicting the properties of pharmaceutical dosage forms from the properties of the raw materials they contain. Achieving this with reasonable accuracy would aid the faster development and manufacture of dosage forms. A variety of approaches to prediction or correlation of properties are reviewed. These approaches have variable accuracy, with no single technique yet able to provide an accurate prediction of the overall properties of the dosage form. However, there have been some successes in predicting trends within a formulation series based on the physicochemical and mechanical properties of raw materials, predicting process scale-up through mechanical characterisation of materials and predicting product characteristics by process monitoring. Advances in information technology have increased predictive capability and accuracy by facilitating the analysis of complex multivariate data, mapping formulation characteristics and capturing past knowledge and experience.
In a recently drafted "Note for guidance" of the European Community it is stated that "The therapeutic objective and rationale for developing the prolonged release product should be provided". This implies that any therapeutic claim should be documented by ad hoc clinical trials. Another "Note for guidance" describes "the studies to be conducted in man, which are specific to new extended release forms containing recognized active and safe medicinal substances so as to ensure a more prolonged action than the conventional pharmaceutical forms already marketed". From this second "Note for guidance" it appears clearly that three situations must be distinguished: a) a modified release dosage form is intended for use with a new active principle; b) the active principle is already available in a conventional pharmaceutical form; and c) the active principle is available as a modified release dosage form with which the new form is not bioequivalent. In case a) drug development clearly proceeds as with any other new clinical entity, but in addition "the therapeutic objectives and rationale for developing" a prolonged release product must be provided. Unless the reasons appear evident, some forms of comparison with a conventional release form or a solution will probably be needed for marketing authorization to be granted. In case b), recommendations contained in the "Note for Guidance" on clinical testing will have to be followed. For case c) no clear recommendations are available and it would probably be more efficacious to develop a new and bioequivalent modified release dosage form rather than to embark into a full clinical program.(ABSTRACT TRUNCATED AT 250 WORDS)
This study evaluated and optimised the ninhydrin assay as a tool for measuring the in vitro release and dissolution of chitosan from solid dosage forms. The precision and accuracy of the assay for the type of chitosan used in the study were examined by measuring the inter- and intra-sample variation and found to be within acceptable limits. The assay was applied practically to construct a pH/solubility profile for chitosan and subsequently to measure the release and dissolution of chitosan from dosage forms in the presence and absence of a model drug, sodium salicylate. Assay performance was found to be satisfactory over a wide range of physiologically relevant pH values. It is concluded that the ninhydrin assay is an essential aid in the design and testing of solid dosage forms with different chitosan-drug release profiles.
Simvastatin, a highly effective cholesterol-lowering agent, has been widely used for the treatment of hypercholesterolemia. During the development of simvastatin solid dosage form, formulation compositions were constantly varied to define a suitable matrix. A fast and reliable method for the dissolution and release testing of simvastatin was highly desirable to support formulation screening. A second derivative UV spectroscopic method was developed for determination of simvastatin in the tablet dosage form. After carefully choosing a zero-crossing technique of second derivative UV measurement at 243 nm, the selectivity and sensitivity of simvastatin was comparable to the previously developed HPLC method. In comparison with the direct UV method, second derivative UV spectroscopy eliminates the interference from UV absorbing excipients such as ascorbic acid, which often results in a bias of 2-10%. This method is also fast and economical in comparison to the more time-consuming HPLC method regularly used for formulation screening. Finally, this method has been validated to be precise and accurate, and is demonstrated to be an excellent alternative to HPLC method for the dissolution and release testing of simvastatin in the solid dosage form.
The trend to deliver drugs to defined areas of the body involves sophisticated carriers systems. In addition to the in vitro drug release profile one must be aware of the in vivo behaviour of the dosage form and the drug. Gamma scintigraphy is an elegant way to gain insights of the actual in vivo distribution pattern of dosage forms. This technique relies on the use of radioactive tracers included into the medicament and selected so as to enable an optimum detection by a gamma ray camera. The choice of a convenient label enables the in vivo determination of the targeting of the formulation administered through a large number of routes. The present paper reviews applications of gamma scintigraphy for the evaluation of dosage forms administered by the parenteral, rectal, buccal, nasal, pulmonary, and ophthalmic routes.
The possibility of oxatomide as the nasal dosage drug for the therapy of nasal allergy was studied. Oxatomide was well absorbed from the nasal cavity, indicating a high permeability to nasal epithelial layer after nasal administration. Acidic pH condition further enhanced the permeation of oxatomide across Caco-2 monolayers, due to the high solubility at the low pH range. Nasal dosage forms for oxatomide (dextrin form, hydroxypropyl-gamma-cyclodextrin form and the suspension of polyethylene glycol) was, therefore, adjusted to pH 5.0. This pH allowed a high solubility of oxatomide without the irritation to nasal epithelium. The effect of nasal administration of oxatomide was studied on experimental allergic rhinitis in sensitized guinea pig. All dosage forms of oxatomide significantly inhibited the dye leakage into the nasal cavity, and among three forms, dextrin form showed the highest effect. High viscosity of dextrin solution was considered to stabilize the dispersion of oxatomide and enhance the retention in the nasal cavity. These results suggest that oxatomide should be useful as nasal dosage drug for allergic rhinitis.
A specific assay for nitroglycerin dosage forms using high-performance liquid chromatography was developed. Sublingual nitroglycerin tablets are dissolved in 25 ml of water and injected directly into the chromatograph. Chromatographic conditions are: mobile phase, 60% methanol in water; flow rate, 2 ml/min; column, microparticulate reversed phase; and detection, 200 nm. The glyceryl mononitrate and dinitrate degradation products of nitroglycerin are separated from nitroglycerin and can be identified by altering the mobile phase composition of methanol.
Dissolution testing of solid oral dosage forms plays a very important part both in the development of new products and in quality control. A fully automated system for dissolution testing known as AUTO DISS is presented and its components are described. On-line determination of active ingredient concentration is possible with the aid of an integrated automatic sampler in combination with various measuring instruments (UV-vis spectrometry, liquid chromatography and flow injection analysis). The suitability of the system is demonstrated by determination of the dissolution of brotizolam from tablets by FIA and of bepafant from capsules by diode-array spectroscopy.
Problems related with controlled release dosage forms are reported. The need for a standard criteria regarding both nomenclature and dissolution test is pointed out. The purpose is to permit a suitable control of the controlled release characteristics.
A new dosage form, comprising Mitomycin C adsorbed on activated carbon particles (MMC-CH) was studied for its local therapeutic effects on carcinomatous peritonitis. After intraperitoneal transplantation of 10(7) cells of Yoshida sarcoma, drug treatment was given on day 2. The ED50 value on ascites was determined with Litchfield-Wilcoxon's method on day 6. The therapeutic index (LD50/ED50) on ascites in MMC-CH treatment was 3.09 times higher than that in Mitomycin C solution treatment.
The aim of the present study was to evaluate the bioavailability of a new tablet formulation of carbocysteine relative against two other oral carbocysteine containing dosage forms, viz. a syrup and capsules. Plasma levels and urine concentrations of carbocysteine were monitored, following oral administration of all three dosage forms to healthy human volunteers, by direct derivatization of carbocysteine using dabsylchloride and subsequent high performance liquid chromatography. There was no difference in bioavailability of carbocysteine from these dosage forms as expressed by the respective areas under the plasma concentration-time curves and total amounts of unchanged carbocysteine excreted in urine.
The objective of this study was to formulate itraconazole semisolid dosage forms and characterize their physicochemical properties. Itraconazole and excipients such as polysorbate 80, fatty acids, fatty alcohols, oils and organic acids were melted at 160 degrees C. The fused solution was then cooled immediately at -10 degrees C to make wax-like semisolid preparations. Their physicochemical attributes were first characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectrometry. The solubility of itraconazole in semisolid preparations and their dispersability in the simulated gastric fluid were also determined. Our semisolid preparations did not show any distinct endothermic peak of a crystalline form of itraconazole around 160-163 degrees C. This suggested that it was changed into amorphous one, when it was formulated into semisolid preparations. In addition, the distinctive functional peaks and chemical shifts of itraconazole were well retained after processing into semisolid preparations. It could be inferred from the data that itraconazole was stable during incorporation into semisolid preparations by the hot melt technique. In particular, itraconazole semisolid preparations composed of polysorbate 80, fatty acids and organic acids showed good solubility and dissolution when dispersed in an aqueous medium. It was anticipated that the semisolid dosage forms would be industrially applicable to improving the bioavailability of poorly water-soluble drugs.
Results of the development of a solid dosage form containing 200 mg Carbamazepine (CBZ) are presented. Citric acid and low substituted Hydroxypropyl-cellulose (L-HPC) were used as dissolution enhancers of the active ingredient. Granulation the CBZ and citric acid with water has no effect on the dissolution of CBZ, but the granulation with absolute alcohol increases the dissolution rate. This enhancement could be explained with a molecular interaction between the CBZ and citric acid in water-free media. This interaction is indicated by the melting points, IR-spectra and scanning electron microscopy of the materials and granules. Further dissolution enhancement can be reached with L-HPC because of its disintegrating effect on the granules. Application of citric acid and L-HPC together results in extremely fast dissolution of the CBZ.