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Tablets are one of the most popular and preferred solid dosage forms because they can be accurately dosed, easily manufactured and packaged on a large scale, have good physical and chemical stability, and can contribute to good patient compliance given their ease of administration. The ability to match doses to patients depends on the availability of multiple dose sizes and adequate dose-response information. These are not always provided, so splitting of the tablets is sometimes necessary. Tablet splitting is an accepted practice in dispensing medication. It has been used when a dosage form of the required strength is not available commercially. The aim of our study was to compare some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets and to accept or exclude their influence on the obtaining of required dosage. According to the results obtained, we may conclude that tablets from batch "I", "II", "III" and "IV" satisfied pharmacopeial requirements concerning crushing strength, friability, disintegration time and mass uniformity. The hardness testing showed acceptable reproducibility and indicate that the data variation was primarily from the irreversible changes in the structure of tablet samples. The act of compacting powders stores energy within the tablets, by shifting or compressing the intermolecular bonds within the particles. The tablets have a natural tendency to relax once pressure is removed, and this tendency works against the interparticle bonding formed during compression. Hardness testing procedure causes irreversible changes in this structure.

Anthocyanins are effective antioxidants but they have also been proposed to have other biological activities independent of their antioxidant capacities that produce health benefits. Examples range from inhibition of cancer cell growth in vitro, induction of insulin production in isolated pancreatic cells, reduction of starch digestion through inhibition of a-glucosidase activity, suppression of inflammatory responses as well as protection against age-related declines in cognitive behavior and neuronal dysfunction in the central nervous system. However, to achieve any biological effect in a specific tissue or organ, anthocyanins must be bioavailable; i.e. effectively absorbed from the gastrointestinal tract (GIT) into the circulation and delivered to the appropriate location within the body. In this study, we assess the stability of anthocyanins from commercial Black currant (Ribes nigrum L.) juice using an in vitro digestion procedure that mimics the physiochemical and biochemical conditions encountered in the gastrointestinal tract (GIT). The main objective of this work was the evaluation of stability of anthocyanins during in vitro digestion in gastric and intestinal fluid regarding whether appropriate enzyme (pepsin or pancreatin) was added or not. Anthocyanins present in commercial black currant juice remain stable during in vitro digestion in gastric fluid regardless whether pepsin was added into the medium or not. Also, they remain stable during in vitro digestion in simulated intestinal fluid without pancreatin. The stability studies of anthocyanins in the intestinal fluid containing pancreatin indicated reduced stability, which also mainly contribute to slight reduction of total anthocyanins content (-1.83%) in commercial black currant juice.

There are numerous methods of administering drugs to the body, both passive and active. Active methods include the use of penetration enhancers and assisted drug delivery. One of them is sonophoresis (phonophoresis). This term is used to describe the effects of ultrasound on the movement of drugs through intact living skin and into the soft tissues. Although the exact mechanism of sonophoresis is not known, drug absorption may involve a disruption of the stratum corneum lipids allowing the drug to pass through the skin. In the future, drug release systems aided by ultrasound may be able to provide slow release of vaccines. Researchers are currently exploring the applications in various areas like cutaneous vaccination, transdermal heparin delivery, transdermal glucose monitoring, delivery of acetyl cholinesterase inhibitors for the treatment of Alzheimer's disease, treatment of bone diseases and Peyronie's disease and dermal exposure assessment. The possibilities seem endless. Drug administration through skin patches, with the advent and development of ultrasound-mediated transdermal transport, may soon become the name of the game. Besides, taking into account the varied possible applications of sonophoretic transdermal drug transport in the fields of biotechnology and genetic engineering, we can envision a whole gamut of newer technologies and products in the foreseeable future.

Periapical disease is the result of bacteria, their product, and the host response to them. Early histological studies of diseased periapical tissue have not been able to demonstrate viable bacteria in the lesions studied. Recent reports indicate that many of periapical lesions are indeed infected before and after endodontic treatment. The validity and applicability of the microbial delivery overcome many disadvantages that we see with systemic drugs. In this case report we presented a novel approach of managing chronic diffuse periapical lesion of lower molar based on specific selection of intracanal medicament in combination with direct periapical injection. We used bacterial culturing and antibiotic sensitivity test to select specific intracanal medicament, in addition we presented an intraosseous injection technique to locally deliver the selected medicament directly into the periapical lesion. Our findings are encouraging and promising. The validity and applicability of the technique needs to be tested in a well controlled clinical trial.

When considering single-dose preparations, it is fundamental that the patient receives in his individual dose an amount of drug close to that claimed on the label. Since drug content and content uniformity of single-dose preparations depend on a number of processes associated with their manufacture, it is obviously unrealistic to expect every unit of product to possess exactly the same amount of the active ingredient. For that reason, pharmacopeial standards and specifications have been established to provide limits for permissible variations in the amount of active ingredient of individual single-dose units. The aim of our study was to determine the applicability of content uniformity and dissolution variation test on ropinirole hydrochloride tablets. According to the results obtained, we may conclude that analyzed ropinirole hydrochloride tablets satisfied pharmacopeial requirements concerning content uniformity and dissolution testing. In this case RSD tended to increase with the decrease of the labeled strength. It is obvious from the R2 value, as well. On the other side, if consider larger number of lots, analyzed by different assay methods and various sample preparation procedures this correlation is less pronounced. This may be a consequence of different assay techniques applied, HPLC, UV-D1 or UV.

Stability testing of an active substance or finished product provides information of the variation of drug substance or final product with time influenced by a variety of environmental factors such as temperature, humidity and light. Knowledge gained from stability studies enables understanding of the effects of the environment on the drugs. The aim of our study was to determine the stability of cefuroxime axetil oral suspension at different temperature storage conditions (stored at room /20 degrees C/ and refrigerated /5 degrees C/ conditions). Determination of cefuroxime (as cefuroxime axetil) was performed by dissolution testing. Fractions of the released cefuroxime axetil were compared using f2 value. After interpolating data for dissolution profiles at room and refrigerated conditions the following f2values were obtained: 62,56; 56,32 and 36,18 on 3rd, 6th and 10th day, respectively. These values indicate similarities in drug release from analyzed cefuroxime axetil oral suspension on 3rd, 6th day, and differences on 10th day. Based on our results, we may assume that cefuroxime axetil oral suspension preserves its stability for 10 days after reconstitution under room and refrigerated conditions. It is obvious, according to the f2 value obtained on the 10th day, that there is a difference between the released cefuroxime axetil from oral suspension at room (87,68%) and refrigerated (92,35%) conditions. Concentration changes can be caused by the mechanisms associated with drug release and hydrolytical decomposition of the sample and higher temperatures during longer period of storage.

Dose-related adverse effects of medications are a major problem in modern medical practice. The "correct" dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril- hydrochlorothiazide scored tablets labeled to contain 20/12.5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12.5 mg in the whole tablet) were: 49.60 +/-3.29% and 49.29+/-0.60 % (lisinopril); 50.33+/-3.50% and 50.69+/-1.95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy.

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmacopeial test for similarity of dissolution profiles ( f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response.

E. Vranić, O. Planinšek, Andrijana Tivadar, S. Hadžović, S. Srčič

For the majority of the pharmaceutical dosage forms, the substances that are used maintain solid state under the standard storage conditions, i.e. powders. The interactions of pharmaceutical powders (active ingredient(s) and excipients) with liquids and vapors (particularly aqueous solutions and their vapors) occur almost always during the production process. From the physical point of view, the interactions among individual components may differ from the expected because chemically identical substances obtained from different producers vary very much. These differences influence either the production process and/or the pharmaceutical form properties. In order to overcome these problems it is necessary to establish a control over the physico-chemical properties of the used materials. The aim of this work was to determine physico-chemical properties of three powder clindamycin phosphate samples (labeled as sample S(1), S(2) and S(3)) acquired through different suppliers. All the analysis were made for the purpose of establishing possible differences among the tested samples that showed variable physical stability in the solution: recrystallization of the S(3) sample in the aqueous solution has been established during storage under standard conditions. On the basis of the obtained data it was possible to recognize the differences among the tested clindamycin phosphate samples and to explain the anomalous behavior of one sample. The surface free energy components for the investigated clindamycin phosphate samples were determined using Wu and Good- van Oss method. The investigated clindamycin phosphate samples exhibit certain differences in surface free energy values as well as in surface morphology and thermal behavior. Comparison of alpha + and alpha - values leads to the conclusion that all three clindamycin phosphate samples perform as monopolar, more electron acceptors, i.e. Lewis acids. However, an important difference exists between samples S(1) and S(2) on one and S(3) on the other side. Sample S(3) exhibits stronger acidic behavior, what could be connected with its recrystallization during the storage. The samples S(1), S(2) and S(3) have different melting points e.g. "onset" temperatures. When the melting points move towards 200 (o ) C, the width of the "onset" temperature peak is especially important. In the case of wider peak, the potential for recrystallization seems to be higher. According to the stated, the sample S1 would be the "sample of choice" for the formulation of the stable pharmaceutical dosage form and has not shown any recrystallization tendencies during the storage period.

In order to achieve the multi-claim products required for the dental care category, it is necessary for the formulator to use a variety of different ingredients. This places a number of demands on the development process. Innovations in the areas of pharmaceutical technology have contributed to the formulation of the products having superior efficacy as well as other attributes that may contribute to clinical response and patient acceptability. Improved clinical efficacy and tolerability, along with conditioning signals, should encourage patient compliance with oral hygiene further complementing professional efforts directed at disease prevention. The most effective way of preventing the development of dental disease is in controlling the production of dental plaque. It is formed by microbial action. The removal of plaque from the teeth and related areas is essential for the maintenance of a healthy mouth. In this paper we have presented the main components of toothpastes and mouthwashes. For the active ingredients, their supposed effect as therapeutic agents is also explained.

Amorphous forms are, by definition, non-crystalline materials which possess no long-range order. Their structure can be thought of as being similar to that of a frozen liquid with the thermal fluctuations present in a liquid frozen out, leaving only "static" structural disorder. The amorphous solids have always been an essential part of pharmaceutical research, but the current interest has been raised by two developments: a growing attention to pharmaceutical solids in general, especially polymorphs and solvates and a revived interest in the science of glasses and the glass transition. Amorphous substances may be formed both intentionally and unintentionally during normal pharmaceutical manufacturing operations. The properties of amorphous materials can be exploited to improve the performance of pharmaceutical dosage forms, but these properties can also give rise to unwanted effects that need to be understood and managed in order for the systems to perform as required.

Excipients are generally considered inert additives included in drug formulation to help in the manufacturing, administration or absorption. Other reasons for inclusion concern product differentiation, appearance enhancement or retention of quality. Excipients can initiate, propagate or participate in chemical or physical interactions with an active substance, possibly leading to compromised quality or performance of the medication. Understanding the chemical and physical nature of excipients, the impurities or residues associated with them and how they may interact with other materials, or with each other, forewarns the pharmaceutical technologist of possibilities for undesirable developments.

Different imaging techniques are used to pick up the signal of interest in digital sensors, including charge-coupled devices (CCD), complementary metal-oxide semiconductors (CMOS), photostimulable phosphors plates (PSP) and tuned-aperture computed tomography (TACT) Digital radiography sensors are divided into: storage phosphor plates (SPP) called photostimulable phosphor plates (PSP), silicon devices such as charge-coupled devices (CCD) or complementary metal oxide semiconductors (CMOS). Relatively new type of imaging that may hold advantage over current radiographic modalities is tuned-aperture computed tomography (TACT).

The endodontium and periodontium are closely related and disease of one may lead to secondary disease in the other. The differential diagnosis of endodontic and periodontal disease is of vital importance, so that the appropriate treatment can be done. Microorganisms play a primary role in endodontic and periodontal infections. The magnitude of the host response will be directly proportional to the virulence and the number of microbial cells present. Tissue damage caused by bacteria is mediated by either direct or indirect mechanisms. Direct harmful effects caused by bacteria involve their products, such as enzymes (collagenase, hyaluronidase, condroitinase, acid phosphatase), exotoxins and metabolites (bytrate, propionate, ammonium polyamines, sulphured compounds). In addition, bacterial components such as peptidoglycan, teichoic acid, fimbriae, outer membrane proteins, capsule, and lypopolysaccharide, stimulate the development of host immune reaction capable of causing severe tissue destruction.

Endodontic pathology is a bacterial disease. It is well established that periapical disease is the result of bacteria, their product, and the host response to them. Periradicular disease will occur after microorganisms and their metabolic products affect the periradicular tissue. Aim of using antibiotics as part of a treatment regimen is to achieve, within the periodontal environment, a concentration of the drug that is sufficient either to kill (bactericidal) or arrest the growth (bacteriostatic) of pathogenic microorganisms. There are two possible approaches to improve the drug action: sustained and controlled drug release to reduce or eliminate side effects by improving the therapeutic index and site-specific drug delivery to minimize systemic effects. These two strategies have been explored by the association of drugs with different vehicles, either naturals or synthetics. A wide variety of specialized local delivery systems (i.e.intrapocket devices) have been designed to maintain the antibiotic in the GCF (gingival crevicular fluid) at a concentration higher than the MIC (minimum inhibitory concentration). Fibres, films, strips and microparticles made of biodegradable or non-biodegradable polymers have been reported as effective methods to administer antibacterial agents for periodontal therapy. Together with these solid devices, semisolid adhesive or non-adhesive formulations have also been proposed.

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