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Background and Purpose: Oral administrations have been used for many years as a main method comparing to other methods. Sustained release techniques have been a great interest recently. Matrix polymers are one of the ways used to prepare a sustained-release drug and are most widely used to prepare the controlled-release drugs. Cellulose derivatives are the most common ones. Solubilities of some drugs are pH-dependent due to their acidic or basic nature. Diltiazem Hydrochloride due to having a pH-dependent solubility is a suitable model to investigate the effect of pH and also to prepare pH-independent formulations.
Materials and Methods: In the present study, an attempt was made to form pH-independent formulations using HPMC, lactose, CAP and organic acids in different ratios. The physicochemical properties of tablets prepared (including weight uniformity, hardness, tensile strength, friability and assay) were investigated. Rate of drug release was studied using USP I at pH 1.2 and 7.2, and sampling was done in the time of 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8. The drug release data were analyzed according to four kinetics models.
Results: Drug release profile in acid free formulations showed that it was higher in the acidic medium. 50% replacement of HPMC with CAP and 1:1 ratio with drug release was pH-independent. Studying the formulations containing organic acids citric acid and polymer with 1:1 and 2:1 ratios ascorbic acid and polymer with 1:1 and 2:1 ratios and tartaric acid with 1:1 and 2:1 ratios showed their pH independent release characteristics.
Conclusion: These results showed the effect of combination of polymers and organic acids on drug release and its kinetic. Thus, the micro-environmental conditions for the dissolution and diffusion of diltiazem HCl were almost kept constant. The release of diltiazem HCl from tablets composed of HPMC and organic acids was found to be pH-independent.

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Background and purpose: The increasing effect of liquisolid systems on dissolution behavior of poor soluble drugs has been proved. In this research, the effect of glycerin, as a nonvolatile solvent, on release profile of indomethacin was evaluated.
Materials and methods: The Avicel as carrier and silica as coating powder material in 20: 1 ratio were used. Indomethacin was dispersed in glycerin with different ratios. The binary mixtures of Avicel and silica were added to the mixture containing the drug and glycerin under continuous mixing. Starch as disintegrate was mixed with all formulations for a period of 10 minutes. After preparing several formulations, the release profiles were evaluated. To evaluate any interaction between indomethacin and the other components in liquisolid formulations, the differential scanning calorimeter (DSC) was used.
Results: The results showed that liquisolid formulations exhibited significantly higher drug dissolution rates in comparison with directly compressed tablet. The enhanced rate of indomethacin dissolution from liquisolid tablets was probably due to an increase in wetting properties and surface area of drug particles available for dissolution. Also, it has been shown that the fraction of molecularly dispersed drug (FM) in the liquid medication of liquisolid systems was directly proportional to their indomethacin dissolution rate (DR). An attempt was made to correlate the percentage drug dissolved in 10-minutes with the solubility of indomethacin in glycerin.
Conclusion: The liquisolid compacts technique can be a promising alternative for the formulation of water insoluble drugs, such as indomethacin into rapid release tablets.

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Background and purpose: The pharmaceutical excipients can be incompatible with drug or other excipients. Thus, for each material, compatibility with formulation components and packaging materials should be examined. The dissolution of a drug has an important role in its bioavailability. Any change in the physico-chemical properties can result in changes in the drug release, and furthermore in its bioavailability. In order to overcome such changes, it is necessary to determine the storage conditions required for obtaining a desired drug release. The aim of this study was to investigate the effects of time and environmental factors on the physical properties of piroxicam tablets. Materials and methods: Piroxicam tablets were prepared by the direct compression method and using different excipients. After conducting some initial tests, these tablets were subjected in different temperatures and humidities for six months. Drug release and disintegration time were analyzed in periods of study (baseline, 3, and 6 months). DSC (differential scanning calorimeter) and FTIR (fourier transform infrared) were used to determine the possible interactions between drug and excipients. Results: The results of drug release from different formulations after 3 and 6 months storage in 25° C /60% RH and 40° C /75% RH showed statistically significant difference among various times. Under all storage conditions piroxicam tablets showed an increase in disintegration time. DSC and FTIR did not show any interaction between formulation ingredients. Conclusion: The results of dissolution and disintegration time showed that keeping piroxicam tablets for three and six months in different conditions caused significant changes in the drug release and disintegration time. Moreover, no change was observed in the physical stability of tablets.

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Background and purpose: The gastroretentive drug delivery systems can be retained in the stomach due to low bulk density. This assist in improving the oral sustained delivery of drugs that have an absorption window in a particular region of the gastrointestinal tract. These systems release the drug content before reaching the absorption site and provide optimal bioavailability. Several approaches are currently utilized to prolong gastric retention time. These include floating systems, polymeric bioadhesive, and swelling and expanding systems. The objective of this study was to develop and characterize gastroretentive floating matrix tablets from propranolol HCl. Materials and methods: Propranolol floating matrix tablets, containing HPMC K15M or Carbopol and gas-generating agent were prepared using direct compression method. The drug release profile of tablets was evaluated based on USP method. The in vitro floating characteristics of these tablets were studied in pH 1.2. Results: The release rate decreased when the amount of polymer increased. The drug release also increased in the presence of gas-generating agent. The results showed that tablets containing HPMC had better floating properties than tablets containing Carbopol. Adding gas generating agent to the formulations modified the floating properties of matrices. Conclusion: These results proved the effect of polymers and floating agents on drug release profile. The use of HPMC K15M and gas-generating agents can lead to suitable floating formulation of propranolol HCl.

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Background and purpose: One of the methods of preparing controlled-release dosage forms is the incorporation of drug in a matrix containing a hydrophilic rate-controlling polymer. Drug-polymer ratio, drug particle size and HPMC particle size have been identified as modifiers of drug release. This study evaluated the relationship and influence of formulation factors such as drug-HPMC ratio and particle size of drug and HPMC on drug release from matrices containing HPMC K 15 M and thophylline as model drug. Materials and methods: Theopylline tablets were obtained by the direct compression method using different particle sizes and ratio of theophylline and HPMC K15M. The physicochemical properties of prepared tablets were investigated. Drug release rate was also studied using USP I dissolution apparatus at pH 1.2 and 7.2. From different formulations the theopylline release was analyzed and then the data was fitted to Kinetic models. Results: The results of the present study showed that the rates of theophylline release from HPMC K15 M matrices are mainly controlled by the drug-HPMC ratio. The drug and HPMC particle size also influenced the drug release parameters, although to a lesser extent. Conclusion: The main factor influencing the drug release from formulations is the polymer content. There is direct relationship between the polymer particle size and drug release. However, there is an inverse relationship between the drug particle size and release of theophylline.

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Background and purpose: Oral route is the most frequently used route for drug administration and tablets are the most popular oral drug forms. The study of drug-excepient compatibility is an important process in development of a stable solid dosage form. Incompatibility between drugs and excipients can alter the stability and bioavailability of drugs, thereby affecting its safety and/or efficacy. In this study, the effects of formulation ingredients under aging and environmental factors on physical properties of atenolol tablets were evaluated. Materials and methods: Atenolol tablets were obtained by the Direct Compression method and using different excepients. After conducting some initial tests, tablets were subjected indifferent temperatures and humilities for six months. From different formulations, the atenolol release and disintegration time were analyzed. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were used to determine the possible interactions between drug and excipients. Results: The results of drug release from different formulations after 3 and 6 months storage in 25°C/60% relative humidity (RH) and 40°C/75%RH showed significant differences among various times. Under all the storage conditions, atenolol tablets showed an increase in disintegration time. DSC and FTIR did not show any interaction. Conclusion: The results of dissolution and disintegration time showed that keeping atenolol tablets for three or six months in different conditions caused significant changes in the drug release and disintegration. Moreover, no change was observed in the physical stability of tablets.

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Background and purpose: Risk of pathogen transmission through poor quality cosmetic products that are illegally smuggled is very high. In this study the microbial contamination of some foundation creams obtained from poor quality markets and a sample obtained from pharmacy were investigated. Materials and methods: In this study the microbial content (bacterial total count, fungal count, and presence of Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacter) of all samples were evaluated using pour plate and multiple tube techniques Results: The samples were 83.33% contaminated. Fungal contamination in was observed in 42.8% of total samples. All samples were found contaminated by pathogenic microorganisms and Staphylococcus aureus was observed to be the most preponderant. Conclusion: High level of contamination in foundation creams, threatens the health of consumers. These results indicate that high levels of contaminants are found even in raw materials used for preparation of cosmetic products. Contaminations in all processes of producing, packing, and storing of such products call for a more active involvement of quality assurance system in cosmetic industry.

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Background and purpose: In Situ Gel dosage forms are successfully used as drug delivery systems to control drug release and protect the medicaments from a hostile environment. The aim of this study was to formulate and evaluate in situ oral topical gels of fluconazole based on concept of pH triggered system. Materials and methods: An in situ gel system consisting of carbopol 934, hydroxypropyl methylcellulose and sodium alginate was used in different concentrations to prolong the release of fluconazole. Fluconazole was added to polymer’s solution after being hydrated. Formulations were evaluated for gelling capacity, physical stability, pH, drug content, viscosity and in vitro release. Results: The use of carbopol as in situ gel forming agent was substantiated by the property to transform into stiff gels when the pH was raised. The gelling capacity, pH and drug content of formulations were found to be satisfactory. The viscosity range was from 60 to 104 centipoise in shear rate of 20 rpm. The formulations showed pseudoplastic flow and were able to release the drug slowly. The formulations showed no significant changes in different condition during the period of 90 days and were found to be stable. Conclusion: The ideal formulation can be utilized for the sustained release property.

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Background and purpose: In ocular delivery the physiological constraints imposed by the protective mechanisms of the eye lead to low absorption of drugs, resulting in a short duration of the therapeutic effect. Thus using in-situ gelling systems could increase the residence time of the drug in the eye. These systems are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac. The aim of this study was to formulate and evaluate an ophthalmic delivery system for diclofenac sodium (a nonsteroidal anti-inflammatory drug), based on the concept of ion-activated in situ gelation. Materials and methods: Ion-activated in situ gelling systems (sodium and calcium) consisting of sodium alginate and hydroxyl propyl methyl cellulose were prepared in different concentrations under aseptic condition. Diclofenac sodium was added after hydration. Formulations were evaluated for gelling capacity, physical stability, pH, drug content, viscosity and in-vitro drug release. Results: The clarity, pH and drug content of the developed formulation were found to be satisfactory. The developed formulation was stable and provided sustained drug release over an 8-h period. The viscosity was found to be in the range of 29 to 63 centipoise in shear rate of 20 rpm. The formulations showed pseudoplastic flow behavior. The ideal formulation showed no significant changes during a 90-day period and was found stable. Conclusion: The developed formulation can be used as an in-situ gelling vehicle to enhance ocular bioavailability and the reduction in the frequency of instillation, thereby resulting in better patient compliance.

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Background and purpose: There is a high risk of pathogen contamination in poor quality cosmetic products that are illegally smuggled into our country. Such contaminations can be easily passed to consumers and endanger their health. In this study the microbial contamination were investigated in some nonstandard moisturizing creams found in poor quality markets and standard creams from drug stores. Materials and methods: The study included nine samples of moisturizing creams obtained from poor quality markets and three samples placed on drug stores and standard markets. The samples were evaluated for microbial content (bacterial total count, fungal count, and presence of Pseudomon asaeruginosa, Staphylococcus aureus and Entrobacter) using pour plate and multiple tube techniques. Results: Aerobic bacteria counts in all samples were more than cfu.g-1 1000. Fungal contamination was seen in 17% in non-standard samples and in 67% in standard creams which were again more than cfu.g-1 1000. All samples were found contaminated by entrobacters. Staphylococcus aureus was observed in three samples of nonstandard and two samples of drug stores. We detected P. aeoroginosa in three samples of nonstandard and one sample of standard moisturizing creams. Conclusion: High level of contamination in moisturizing creams would influence the health of consumers. It is believed that low grade raw materials and insufficient manufacturing surveillance in production process are amongst the main reasons for microbial contamination in cosmetic products. Hence, more supervision is needed to control such problems.

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Background and purpose: Solid lipid nanoparticles are in the colloid carriers. The benefits of these drug carriers are the controlled release of the drug and the protection of the drug being loaded. Spironolactone is an aldosterone antagonist and androgen receptor. Its oral bioavailability is low due to the low solubility of this drug and its slow release. Reducing particle size by increasing the level of the drug leads to increased release, higher oral bioavailability, higher particle size in contact with the dissolution medium, and increasing the dissolvability of the drug saturation.
Materials and methods: Solvent emulsification/evaporation was used to prepare spironolactone nanoparticles. For this purpose, the lipid and drug were dissolved in an appropriate organic solvent and added to the aqueous phase containing surfactant during mixing by homogenizer. After coated with chitosan, the chitosan was dissolved in dilute acid and was added to the suspension on the stirrer drop by drop.
Results: By maintaining the amount of lipid in the formulation and increasing the amount of surfactant, the particle size decreased significantly. In general, the coating of spironolactone nanoparticles with chitosan increased the particle size and their dispersion, and the zeta potential changed from a negative value to a positive value.
Conclusion: Spironolactone coated with chitosan was found to have a slower release than solid lipid nanoparticles and nanosuspension.
 

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Background and purpose: The dissolution of a drug has a major role on its bioavailability. Any change in physico-chemical properties can result in changes in drug release, and furthermore in its bioavailability. Evidence suggest that physicochemical properties of medicinal solids depend on the presence of heat and humidity. In order to overcome such changes, it is necessary to determine the storage conditions required for obtaining a desired drug release.
Materials and methods: Theophylline tablets were prepared by Direct Compression method using Carbapol 934 and HPMC K15M. After conducting some initial tests, the tablets were subjected to different conditions of temperature and humidity for six months. Theophylline release from different formulations was analyzed. The data were then fitted to Kinetic model. Differential Scanning Calorimetry (DSC) was used to determine the physical stability of tablets and possible adverse interactions between drugs with polymers or other materials.
Results: The results of drug release from different formulations showed no significant differences between various times (zero, three, and six months) (P= 0.207). Also, by studying the Dsc thermogram of different formulations the peak Theophylline was seen at approximately 275°C, and the thermogram did not show any changes.
Conclusion: In this study, keeping Theophylline tablets for three and six months in different conditions did not cause significant changes in drug release. Moreover, no change was observed in the physical stability of tablets.
 

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Background and purpose: Psoriasis is an autoimmune inflammatory disease with major skin involvement. Calcipotriol as a vitamin-D analogue is one of the common drugs for topical treatment of psoriasis. Local drug delivery, due to higher concentration of drug at the sites of inflammation, is more effective and causes fewer systemic side effects. Limited skin penetration and durability of common topical formulations reduce the efficacy of treatment. In this study, we aimed to investigate the effect of solid lipid nanoparticles loaded with calcipotriol on local drug delivery.
Materials and methods: In the present study, which is an interventional in vivo study, Solid Lipid Nanoparticle (SLN) was prepared by melting method and mixed with semi-solid base (cream). Then the effectiveness of the final formulation was investigated on the psoriasis model induced by imiquimod 5% in BALB/c mice. Three groups were included in this investigation: negative control (no treatment), positive control (conventional calcipotriol cream), and SLN (SLN cream with calcipotriol).
Results: The results of the present study showed that, the SLN cream significantly reduced inflammatory scores compared to the other two groups on day five (P<0.0001). In addition, drug loading into SLN significantly increased the rate of healing and reduced inflammation.
Conclusion: This study showed that calcipotriol loading with SLN can improve the quality and the rate of treatment of skin lesions caused by psoriasis.