Hongkee Sah

Surfactant effects upon dissolution patterns of carbamazepine immediate release tablet.

The objective of this study was to investigate the effects of sodium lauryl sulfate upon the saturation solubility of carbamazepine, its dissolution kinetics, and T50% defined as the time required for dissolving 50% of carbamazepine. Water, 0.1N-HCI, and phosphate buffers at pH 4.0 and 6.8 containing 0.1, 0.5, 1, and 2% sodium lauryl sulfate were used as dissolution media. The dissolution study was conducted by using the USP dissolution apparatus II with an agitation rate of 75 rpm. Samples of the dissolution media were taken in 7, 15, 30, 45, 60, 75, and 90 min, and the amounts of carbamazepine were determined spectrophotometrically at 285 nm. All dissolution data were fitted well into a four-parameter exponential equation:Q = a(1 — e-bxt)+c(1 — e-dxt). In this equation Q represented % carbamazepine dissolved at a time t, anda, b, c, andd were constants. This equation led to the calculation of dissolution rates at various time points and T50%. It was found that the dissolution rate of carbamazepine was directly proportional to the aqueous concentration of sodium lauryl sulfate. In addition, under our experimental conditions T50% values ranged from 37.8 to 4.9 min. It was interesting to note that T50% declined rapidly as the surfactant concentration increased from 0.1 to 0.5%, whereas it declined more slowly at concentrations greater than 1 %. These results clearly demonstrated that the dissolution rate of carbamazepine and duration of its dissolution test could be tailored by optimizing the amount of sodium lauryl sulfate in a dissolution medium.

Physicochemical Characterization of Diclofenac Sodium-Loaded Poloxamer Gel as a Rectal Delivery System with Fast Absorption

Abstract Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.

Development of new reverse micellar microencapsulation technique to load water-soluble drug into PLGA microspheres

The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.3 to 0.75 g of PLGA, and microspheres were prepared following a modified solvent quenching technique. As a control experiment, the drug was encapsulated into PLGA microspheresvia a conventional methylene chloride-based emulsion procedure. The microspheres were then characterized with regard to drug loading efficiency, their size distribution and morphology. The reverse micellar procedure led to the formation of free-flowing, spherical microspheres with the size mode of 88 μn. When PLGA microspheres were prepared following the conventional methylene chloride-based procedure, most of tetracycline hydrochloride leached to the aqueous external phase: A maximal loading efficiency observed our experimental conditions was below 5%. Their surfaces had numerous pores, while their internal architecture was honey-combed. In sharp contrast, the new reverse micellar encapsulation technique permitted the attainment of a maximal loading efficiency of 63.19 ± 0.64%. Also, the microspheres had smooth and pore-free surfaces, and hollow cavities were absent from their internal matrices. The results of this study demonstrated that PLGA microspheres could be successfully prepared following the new reverse micellar encapsulation technique.

Relation of dynamic changes in interfacial tension to protein destabilization upon emulsification

The objective of this study was to link conformational changes of proteins at a water/methylene chloride interface to their destabilization upon emulsification. When 4 aqueous protein solutions (bovine serum albumin, β-lactoglobulin, ovalbumin, or ribonuclease) were emulsified in methylene chloride, considerable proportions of all the proteins became water insoluble aggregates. There were also noticeable changes in the compositions of their water-soluble species. A series of water/methylene chloride interfacial reactions upon the proteins was considered a major cause of the phenomena observed. Based on this supposition, the interfacial tension was determined by a Krüss DVT-10 drop volume tensiometer under various experimental conditions. It substantiated that the interfacial tension was high enough to cause the adsorption of all the proteins. Under our experimental conditions, their presence in the aqueous phase resulted in reductions of the interfacial tension by the degrees of 8.5 - 17.1 mN m1. In addition, dynamic changes in the interfacial tension were monitored to compare relative rates at which the adsorbed proteins underwent conformational, structural rearrangements at the interface. Such information helped make a prediction about how easily proteins would denature and aggregate during emulsification. Our study indicated that emulsifying aqueous protein solutions in organic solvents should be handled with care, due to adverse interfacial effects.

Understanding of F 2 Metrics Used to Evaluate Similarity of Dissolution Profiles

Dissolution profile comparsions can be done by virtue of the similarity factor . It is a logarithmic reciprocal square root transformation of the sum of squared error of % dissolution differences between two profiles at several time points. It gives information on the degree of similarity between the two profiles: An value between 50 and 100 suggests the similarity/equivalence of the two dissolution curves being compared. The objective of this report was to provide a careful examination on the metrics in detail. It was shown that values exceeded 50, when relative differences in % dissolved between two products were less than 15% at all time points. The similarity factor value was also found to be greater than 50, in cases when absolute % dissolution differences were below 10% at all time points. Interestingly, the value was changed by the number of the time points selected for calculation. In particular, tended to have higher values, when the metrics used a large number of time points in which % dissolved reached plateau. Finally, since the similarity factor was a sample statistics, it was impossible to infer type I/II errors and sampling error. Despite certain limitations inherited in the metrics, it was easy and convenient to evaluate how similar the two dissolution profiles were.

Application of SUPAC-MR in Processing Postapproval Changes to Modified Release Sold Oral Dosage Forms

The objective of this study was to scrutinize the rationale of SUPAC-MR and its application in processing postapproval changes to modified release solid oral dosage forms. The types of postapproval changes that were primarily covered with SUPAC-MR included variations in the components and composition, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. SUPAC-MR defined levels of postapproval changes that the industry might make. Classification of such categories was based on the likelihood of risk occurrence and potential impact of changes upon the safety and efficacy of approved drug products. In most cases, the changes could be classified into 3 levels. It described what chemistry, manufacturing, and control tests should be conducted for each change level. The important tests specified in SUPAC-MR were batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. It then suggested what type of a filing report should be submitted to the FDA for each change level. In general, level 1 changes could be reported in an annual report, whereas level 2 and/or 3 changes could be submitted in changes-being-effected or prior approval supplements. It could be understood that the purpose of SUPAC-MR was to maintain the safety and quality of approved modified release solid oral dosage forms undergoing certain changes. At the same time, it contributed to providing a less burdensome regulatory process with the manufacturers when they wanted to make postapproval changes. European regulatory agencies also implemented SUPAC-like regulations in handling such changes to drug products. Therefore, in this study a recommendation was made for KFDA and the Korean industry to evaluate thoroughly the usefulness of these guidances and regulations in dealing with postapproval changes to modified release solid oral dosage forms.

Scrutiny Made to SUPAC-IR Dealing with Postapproval Changes in Immediate Release Sold Oral Dosage Forms

The objective of this study was to provide a better understanding of SUPAC-IR and its application in handling postapproval changes to immediate release solid oral dosage forms. Originally, SUPAC-IR was aimed at reducing the regulator burdern of the industry when they were making postapproval changes, but still at maintaining the formulation quality and performance of a drug product. The postapproval changes that were covered under SUPAC-IR included variations in the components ad composition of formulation, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. The guidance defined levels of changes, based on the likelihood of risk ocurrence and potential impact of postapproval changes upon the safety and efficacy of a drug product I suggested what a type of fing report should be submitted to the FDA for each level of change. Chemist, manufacturing, and control tests to be executed were also recommended for each change level The important tests specified in the guidance included batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. However, there have been strong demands on revising the current SUPAC-IR in order to resolve some issues and to improve its usefulness in evaluating postapproval changes to immediate release solid oral dosage forms. In particular, the rigorous requirement of case C dissolution test and the definition of batch size were challenged by both academia and the industry. A revision work was in progress to reflect these inputs and to expand the utility of SUPAC-IR. As a result of these concerted efforts, an updated 2nd version of SPAC-IR would be likely to be issued ver soon to the public.

Development of 13 C-urea-containing capsule for diagnosis of H. pylori

The purpose of this study was to develop a new capsule for diagnosis of H. pylori. The urea-containing capsules were prepared with various diluents such as polyethylene glycol (PEG), microcrystalline cellulose, sodium lauryl sulfate and citric acid. The dissolution test, breath test and stability test were then performed on the capsules. Microcrystalline cellulose and sodium lauryl sulfate retarded the initial dissolution rates of urea. However, PEG increased the initial dissolution rates of urea. Furthermore, two formulae composed of PEG, [ (38/1.9 mg/cap)] and [ acid (38/1.9/1.9 mg/cap)] had the maximum DOB value, about 16 at 20 mim, while the formula composed of only 38 mg had the maximum DOB value at 30 min. The results indicated that PEG improved the, sensitivity of in the human volunteers. The capsule [ (38/1.9 mg/cap)] was stable for at least six months in 25 and . Thus, a PEG-containing capsule, [ (38/1.9 mg/cap)] would be a more economical, sensitive and stable preparation for diagnosis of H. pylori.