Semisolid Pharmaceutical Form Research Articles

Development of semisolid pharmaceutical forms with mometasone furoate

Abstract Objective This study aims to develop semisolid pharmaceutical forms for the topical administration of mometasone furoate. Methods Two creams (O1 and O2) and four hydroxypropyl methylcellulose-based hydrogels were prepared (H3-H6). Two different sorts of hydroxypropyl methylcellulose were used in concentrations of 15 and 20%. Consistency, spreadability, viscosity, and pH were measured. In vitro drug release was determined by a vertical, Franz diffusion cell. Mathematical models were applied for a better understanding of release phenomena. Results O1 and O2 presented lower values for penetration depth and spreadability. Hydrogel viscosity is influenced by the type and concentration of the gel-forming agent. Viscosity decreases in the order H6, H5, H4, and H3. pH varies between 4.6 to 5.92, fulfilling the requirements of European Pharmacopiea. Creams showed 5.49 and 6.59% of mometasone released after 6 hours. The lowest viscosity hydrogel presented the best dissolution of 40.11% mometasone after 6 hours. Conclusions H3 hydrogel releases the highest amount of mometasone furoate after 6 hours. The release is best described by the Korsmeyer-Peppas model explained by water diffusion and polymeric chain relaxation happen during the swelling of the polymer.

Balsam Poplar Buds Extracts-Loaded Gels and Emulgels: Development, Biopharmaceutical Evaluation, and Biological Activity In Vitro.

Balsam poplar buds have been used for wound healing and treating irritated skin in traditional medicine. Balsam poplar buds extracts exhibit anti-inflammatory, antioxidant, and antimicrobial effects. In recent years, scientific research has begun to validate some of these traditional uses, leading to an increased interest in balsam poplar buds as a potential source of natural remedies in modern medicine. The study aims to simulate semi-solid pharmaceutical forms with balsam poplar buds extract and evaluate their quality through biopharmaceutical research. The active compounds identified in Lithuanian poplar buds were p-coumaric acid, cinnamic acid, caffeic acid, galangin, pinocembrin, pinobanksin, and salicin. In gels, pH values ranged from 5.85 ± 0.05 to 5.95 ± 0.07. The determined pH values of emulgels ranged from 5.13 ± 0.05 to 5.66 ± 0.15. After 6 h, the release of active compounds from gels and emulgels ranged from 47.40 ± 2.41% to 71.17 ± 3.54. p-coumaric acid dominates in the balsam poplar buds extracts. The pH values of the prepared sem-solid pharmaceutical forms are suitable for use on the skin. The viscosity of the formulations depends on the amount of gelling agent. All formulations showed antioxidant activity. It is relevant to conduct a more extensive study on the influence of the chosen carrier on the release of active compounds from semi-solid formulations with an extract of balsam poplar buds.

Semi-Solid Dosage Forms Containing Pranoprofen-Loaded NLC as Topical Therapy for Local Inflammation: In Vitro, Ex Vivo and In Vivo Evaluation.

Pranoprofen (PRA)-loaded nanostructured lipid carriers (NLC) have been dispersed into blank gels composed of 1% of Carbomer 940 (PRA-NLC-Car) and 3% of Sepigel® 305 (PRA-NLC-Sep) as a novel strategy to refine the biopharmaceutical profile of PRA, for dermal administration in the treatment of skin inflammation that may be caused by possible skin abrasion. This stratagem intends to improve the joining of PRA with the skin, improving its retention and anti-inflammatory effect. Gels were evaluated for various parameters such as pH, morphology, rheology, and swelling. In vitro drug release research and ex vivo permeation through the skin were carried out on Franz diffusion cells. Additionally, in vivo assays were carried out to evaluate the anti-inflammatory effect, and tolerance studies were performed in humans by evaluating the biomechanical properties. Results showed a rheological profile common of semi-solid pharmaceutical forms for dermal application, with sustained release up to 24 h. In vivo studies using PRA-NLC-Car and PRA-NLC-Sep in Mus musculus mice and hairless rats histologically demonstrated their efficacy in an inflammatory animal model study. No signs of skin irritation or modifications of the skin's biophysical properties were identified and the gels were well tolerated. The results obtained from this investigation concluded that the developed semi-solid formulations represent a fitting drug delivery carrier for PRA's transdermal delivery, enhancing its dermal retention and suggesting that they can be utilized as an interesting and effective topical treatment for local skin inflammation caused by a possible abrasion.

CRITICAL EQUIPMENT QUALIFICATION PARAMETERS AFFECTING THE HOMOGENIZATION PROCESS OF MEDICAL CANNABIS SEMI-SOLID PHARMACEUTICALS

The medical cannabis has been used for many of years for medicinal purpose, in different pharmaceuticalformulation, mostly as a magistral preparation for the relief of pain in cancer patients or chronical painful diseases.Over than 540 substances were found from which more than 100 that have been found to be cannabinoids due totheir similar chemical structure. The component with the most psychotropic action is Δ9 -tetrahydrocannabinol (Δ9 -THC), and the major non-psychoactive ingredient is cannabidiol (CBD). Δ9 -tetrahydrocannabinol firstly wasisolated in 1969 by Robert Mechoulm and Yechiel Gaoni. In 2003 World Health Organization put Δ9 -tetrahydrocannabinol in Schedule IV of the convention. Several therapeutic indications relate to the Δ9 -THC andCBD as analgesia, inflammatory and neurodegenerative diseases, and many other cases. In some studies, there arereported safety concerns about the registered side effects of Δ9 - THC as a psychoactive. For that reason, the legalusage of cannabis for medicinal purposes and for recreational use is regulated differently. The most relevantexplanation is related to the not enough sufficient results and data obtained from the pharmacokinetic studies andresearch in pharmacological behavior. Extracts of cannabis was used from many years ago. Nowadays inpharmaceutical industry as the development of technology there are many dosage forms in where extracts,cannabinoids, flower are used. Medicinal cannabis products can come in many different forms, including capsules,drops, chewable, creams, crystals, flower, lozenges, oil (most common), oro-mucosal sprays, tinctures and manymore. Also, there are synthetic analogs to nature cannabinoids in pharmaceutical market. In this study will bediscussed about production of semisolid pharmaceutical forms obtained from medical cannabis. They are producedin pharmaceutical grade equipment, high-pressure homogenizer mixer. In this study it will be discussed about theprocess of equipment qualification. Firstly, by the user requirement specification, design qualification protocol wasapproved. Then factory acceptance test was performed in production site of equipment and site acceptance test wasperformed in costumer’s site. Then installation qualification protocol was look through and then operationalqualification protocol also. All the qualification protocols were approved by both sides. In different qualificationprotocols, different tests were performed, and they are explained separately. During the qualification process, thereare considered some of the parameters which later during the production process can affect in the quality of finishedproducts. These parameters are called critical process parameters and accent will be put on this process parametersthat are with a critical effect on quality of the final products. This critical process parameters were considered andconcluded from qualification protocols where all the parameters that can affect quality of the product wereseparately examine.

ANTIMICROBIAL ACTIVITY OF CHELIDONIUM SPECIES MAJUS L.

The present paper has as main objective the determination of the antimicrobial and antifungal activity of some pharmaceutical forms obtained in the laboratory of pharmaceutical technology of the Faculty of Pharmacy of the University "Lower Danube of Galati". We used semi-solid pharmaceutical forms with different concentrations of soft extract of Chelidonium majus L, 50%, 25% and 10% in two ointment bases, simple ointment and base III I performed the antimicrobial activity for all four ointments, compared to extract 1: 3.75 in hydroalcoholic solution (ethyl alcohol / water 35/65 by mass) from aerial parts of Chelidonium majus and alcohol 70 °. hydroalcoholic solution was obtained by cold preparation from the aerial parts of the plant Chelidonium majus. We determined the antimicrobial activity by the diffusimetric method (Kirby-Bauer) and the dilution method. The 50% concentration ointment (UNG A) shows activity on some Gram-negative and Gram-positive bacteria and not on the fungus Candida albicans.

Formulation of Gels and Emulgels with Malus domestica Borkh: Apple Extracts and Their Biopharmaceutical Evaluation In Vitro.

Phenolic compounds that estimate apple extracts with multifaceted biological effects are potentially valuable for protection against skin disorders. The purpose of our research was to formulate gels and emulgels containing a complex of phenolic compounds of apple extracts and to perform a biopharmaceutical evaluation of semi-solid pharmaceutical forms, determining their antioxidant activity in vitro. HPLC analyses of phenolic compounds were performed. The total amount of phenolic compounds found in the sample of apples from the ‘Paprastasis antaninis’ cultivar was 1455.5 ± 72.8 µg/g. The release of phenolics from gels and emulgels was assessed by Franz-type diffusion cells. The in vitro release test revealed that phenolic compounds were released from the gel (G1–G6) formulations (70.6–73.8%) compared to the amounts (77.2–83.9%) released from the emulgel (E1–E6) formulations. The largest amount (83.9%) of phenolic compounds was released from the E5 formulation, while the smallest amounts (70.6%) were released from the formulations G3 and G5. The antioxidant activity evaluated by the DPPH and FRAP methods observed in all gel (G1–G6) and emulgel (E1–E6) formulations after 6 h were the strongest, compared to the activities observed in the formulations after 2 or 4 h. Gels and emulgels, which are rich in apple extracts, have strong antioxidant properties and may be promising choices for the development of new, innovative pharmaceutical forms or cosmetics.

Study and Evaluation of the release of Flavonoids extracted from various Eggplant cones from Semisolid Pharmaceutical Forms (In vitro)

Various semisolid pharmaceutical forms have been prepared from eggplant calyx extract which rich in flavonoids and antioxidants. These ingredients were titrated in the prepared extracts, and then incorporated into the prepared pharmaceutical forms. Eggplant calyxes were used for three varieties cultivated in Syria. The flavonoids were extracted from them by using several aqueous and organic solutions. Three types of extracts were prepared for each type of eggplant (aqueous, ethanolic 70%, methanolic). The ethanolic extract of black eggplant showed the highest content of flavonoids. The black eggplant extract contained the largest amount of flavonoids in the three types of extracts. The antioxidant capacity of the plant extracts was measured by measuring its ability to remove free radicals of the fixed root DPPH, and the ethanolic extract of the black eggplant showed the best antioxidant capacity. Three topical pharmaceutical formulas were prepared of the ethanolic extract 70% for the rectangular black eggplant calyx, and the kinetics of the release of the main components from them in vitro was studied using a Franz cell, within four hours to determine the release model for each formulation in order to compare the formulas and select the best one. The cream of the (o / w) pattern gave the best release of the active substances because it released the highest percentage (92%) after two hours and the release pattern was of the zero order, while the rest of the formulas had the highest percentage of release after four hours with some deficiency of the active substances in them.

Formulation and Preparation of a Novel Toothpaste Using the Essential Oil of Salvia officinalis

Dalmatian Sage(Salvia officinalis L., Lamiaceae) is known in the Middle East for its therapeutic properties, and is widely used in folk medicine, cosmetics, flavoring and preservative for food products. It’s essential oil possess antimicrobial, antiviral, antifungal and antioxidant properties so that it is widely used to treat gingivitis and laryngitis. The present study has formulated a semi-solid pharmaceutical form (tooth paste) that contains essential oil extracted from the leaves of common sage and conducted the necessary observations and further control tests, in preface for preparation at the industrial level at the later stage. The Sage leaves were harvested from al-Qadmus area, in Tartous province, Syria, dried and extracted for essential oil by hydro-distillation. The extraction yield was estimated to formulate the toothpaste and observational tests for quality control (sensory tests, the absence of solid and sharp particles, spread ability, pH, moisture content, bacterial tests and stability test on shelf) were performed. Our formulated toothpaste characteristics were identical to the commercial toothpaste specifications from the following respect: Sensory tests, spread ability, pH, moisture content and stability on shelf, also the microbial parameters values were within permissible limits. Our study suggest using this formula to prepare a tooth paste with sage essential oil and perform further studies to evaluate its efficacy on dental cavities and gingivitis.

Clove essential oil encapsulated on nanocarrier based on polysaccharide: A strategy for the treatment of vaginal candidiasis

This work aims to formulate a new semisolid pharmaceutical form based on clove essential oil and polysaccharides for the treatment of vaginal candidiasis. The nanoemulsions showed excellent colloidal stability with values of zeta potential higher than 30 mV in module, as well as hydrodynamic diameter between 198.8 and 321.0 nm and moderate polydispersity. The nanosystems did not show macroscopic instability phenomena and demonstrated adequate pH values for vaginal use. The presence of clove essential oil in the nanoemulsion was attested by a UV-Vis spectrophotometer with encapsulation efficiency greater than 99%. Emulsions based on carboxymethylcellulose and alginate (Ecmc and Ealgi, respectively) showed ferrous ion chelating ability in a range of 42-62%, with results superior to those of ascorbic acid. Ecmc formulation exhibited a higher inhibitory effect against Candida albicans and higher content of essential oil, being used in the formulation of emulgel. The rheological properties of the emulgel showed a non-Newtonian behavior, pseudoplastic type, with values of G' higher than G”, which characterizes the formation of a gel. The micrographs obtained by Scanning Electron Microscopy (SEM) showed the incorporation of the nanoemulsion in the polymeric matrix, whose diameters corroborated with the results obtained by dynamic light scattering.

Incorporación de un novedoso complejo de tinidazol con propiedades antimicrobianas a dos formas semisólidas de uso tópico

The increase in bacterial resistance to antibiotics commonly used for the treatment of skin infections, highlights the need to find alternative and effective medications, capable of counteracting this health problem that not only involves a region, but has become A global health problem. It has been shown that a novel complex based on tinidazole and copper ([Cu(tnz)2 (NO3) 2]) has good antimicrobial activity, however, so that it can be used as an alternative for topical use, it must have the characteristics necessary for it to be incorporated into a formulation that allows its application. Bearing in mind that semi-solid pharmaceutical forms constitute the most commonly used group within dermatological formulations; Two types of formulations, one type cream and one cream-gel, were prepared in order to verify in which of them the complex [Cu(tnz)2(NO3)2] is conveniently incorporated. For both formulations the organoleptic properties, pH, extensibility area, viscosity, and particle size were determined. The results obtained show the advantages of the cream-like formulation compared to the cream-gel.

Near-infrared spectroscopy-based methods for quantitative determination of active pharmaceutical ingredient in transdermal gel formulations

Semi-solid pharmaceutical forms, like topical and transdermal products, are widely used for medical purposes since they provide convenient and pain-free treatment for patients. In this study, two transdermal gel formulations with different active pharmaceutical ingredients were analyzed with near-infrared spectrophotometers with three distinct optical arrangements (dispersive, Fourier transform, and diode-array spectrophotometers) for the measurement of active pharmaceutical ingredient concentration. The reference concentrations were measured with high-performance liquid chromatography methods.The developing of calibration for reference concentrations based on near-infrared spectra was performed using partial least squares regression. The spectra from near-infrared spectrophotometer with diode-array optical arrangement presented the best root mean square error of cross-validation results with 0.045% and 0.144% for the two active pharmaceutical ingredients. The root mean square error of cross-validation using dispersive spectra were 0.125% and 0.193% and using Fourier transform spectra were 0.130% and 0.344% for the active pharmaceutical ingredients. The results of partial least squares regression were confirmed using simulated spectra based on the measured datasets.Near-infrared spectroscopy can be used successfully for the quantitative measurement of active pharmaceutical ingredient concentration in transdermal gel formulations. The type of optical arrangements of spectrophotometers can influence the performance of calibrations and have to be optimized case by case.

Optimization, physical-chemical evaluation and healing activity of chitosan ointment

Context: Chitosan has received attention as a functional, sustainably renewable, nontoxic and biodegradable biopolymer for pharmaceutical applications such as healing agent. Aims: To design a semisolid pharmaceutical form (ointment), employing 1% chitosan as an active pharmaceutical ingredient. Methods: The formulation was carried out through D-optimal mixing design, with a linear model. Variation components evaluated were the concentration of sodium hydroxide, water and anhydrous lanolin. Variables included those of response pH and extensibility. Three batches were produced, and the physical and chemical stability of the ointment was assessed through stress and shelf-life tests for 24 months. Physical-chemical parameters studied included organoleptic characteristics, chitosan content, rheological behavior, apparent viscosity, pH and extensibility. Wound healing activity was also tested for burns damage model in rats. Results: The mixture design showed that the best formulation was the one containing 0.12% sodium hydroxide, 20.0% anhydrous lanolin and 40.0% water, with the mechanical-structural behavior characteristics of a semisolid product. This product had healing effects and showed adequate physical chemical stability during the time under study. Conclusions: The results of this study suggest that 1% chitosan ointment design favors scarring in the second-degree burn damage model in rats skin applied for 14 days at the rate of daily administration.

Estabilidad de los medicamentos después del primer uso

Context: There are standards that allow establishing the microbiological and physicochemical stability of a medicine; however, beyond use date of drugs depends not only on these criteria, but also on individual institutional characteristics. The multiple factors that involve the allocation of the stability of a medication, if not properly articulated, can lead to therapeutic failures and adverse events in patients. Aims: To design an algorithm to determine the stability beyond use date of a drug in a high complexity healthcare institution. Methods: Pharmaceutical form, packaging, and administration route were defined for each drug. Physicochemical and microbiological stability were assigned to each product. An algorithm was built with the collected information. The stability beyond use date was the shortest time registered between microbiological and physicochemical stability, however, the information of the manufacturer was respected. Results: A total of 938 drugs were analyzed, which 606 (64.6%) were considered as single-dose and 332 (35.4%) as multiple-dose. The mean reason to assign a drug as a single-dose with 90.9% was pharmaceutical form unable to storage, tablet, capsule, and ampoule the most frequent. The main cause with 54.4% to assign a drug as multiple-dose was synthetic products with liquid and semisolid pharmaceutical forms whose packaging materials were allowed to storage after its first use. Conclusions: An algorithm was designed, which can assign the stability beyond use date of drugs using an easy and reliable, generating a more safety use inside the institution.

Compatibility study of tretinoin with several pharmaceutical excipients by thermal and non-thermal techniques

Thermal techniques, such as differential scanning calorimetry, thermogravimetry (TG), derivate of TG curve (DTG), and differential thermal analysis were used as quick screening tools to evaluate the possible interactions between tretinoin (TRET) and excipients used in semi-solid pharmaceutical forms. The non-thermal techniques, fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), and scanning electron microscopy (SEM) were used as a supplementary investigative techniques of possible interactions. The analysis of the FTIR spectra of TRET/excipient binary mixture (BM) was also conducted by a method of Pearson’s correlation, which calculated the difference between the theoretical and experimental FTIR spectra. The TRET, excipients and BM were heated at 200 °C to be analyzed by FTIR and XRD. The physical interactions suggested were mainly observed in the results obtained by thermal techniques with TRET/MTP, TRET/PPP, TRET/CA, and TRET/CTA, but in the TRET/IMD, the FTIR technique shows that there was chemical interaction between these components. The heating of samples changed the chemical structure of the TRET in the TRET/CTA, as well as changed the crystallinity of the TRET in the TRET/MTP and TRET/PPP BM. SEM microphotograph of the mixtures showed no adhesive interfaces in mixtures suggesting that no intense physical interactions between these pharmaceutical raw materials at room temperature.

English

The research and development of new drugs is a slow process that involves costs, requires physical, material and qualified human resources. The purpose of this study was to examine the research of recent years exposed on the challenges and obstacles to production and design of semisolid pharmaceutical forms from extracts or isolated compounds from medicinal plants. This study is an integrative review. The sample consisted of scientific articles found on the databases (Lilacs, Scielo, Science Direct and PubMed) from January 2002 to September 2012. The following descriptors were used: phytomedicines, stability of medicines and pharmaceutical preparations. The design of semisolid pharmaceutical forms, especially those in phytocosmetics, is relevant in Brazil, a major producer country by the pharmaceutical industry. However, due to the peculiarity of each drug and medicine, the study design may become one of the great difficulties of its accomplishment, as well as being a challenge to professionals in developing new pharmaceuticals. Thus, it can be suggested that despite the vast Brazilian biodiversity, there is no investment and cooperation in research and development of new medicines.   Key words: Phytomedicine, drug stability, pharmaceutical preparations.

Compatibility study between hydroquinone and the excipients used in semi-solid pharmaceutical forms by thermal and non-thermal techniques

Thermal techniques, such as differential scanning calorimetry (DSC), thermogravimetry (TG), derivate of TG curve, differential thermal analysis, and non-thermal techniques such as fourier transform infrared (FTIR) spectroscopy and X-ray diffractometry (XRD) were used to evaluate the possible interactions between hydroquinone (HQ) and excipients commonly used in semi-solid pharmaceutical forms. The DSC curve of HQ showed a sharp endothermic event between 173 and 179 °C indicating melting point. No evidence of interaction was observed between HQ and cetyl alcohol (CA), cetostearyl alcohol (CTA), disodium ethylenediaminetetraacetate , and decyl oleate. However, based on the thermoanalytical trials, a physical interaction was suspected between HQ and dipropylene glycol (DPG), glycerin (GLY), hydroxypropyl methylcellulose (HPMC), imidazolidinyl urea (IMD), methylparaben (MTP), and propylparaben (PPP). The FTIR results show that for DPG, GLY, HPMC, MTP, and PPP, there were no chemical interactions with HQ at room temperature, but the heating promotes interaction between HQ and HPMC. The FTIR spectra of HQ/IMD show the chemical interaction at room temperature, which was also observed with heating. The XRD results of mixtures between HQ and DPG, HPMC, IMD, MTP, and PPP indicate no interaction between these substances at room temperature, but the heating modifies the HQ crystallinity in these mixtures. All of these methods showed incompatibility between HQ and the excipient IMD.

Thermal analysis and compatibility studies of prednicarbate with excipients used in semi solid pharmaceutical form

Differential Scanning Calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG) and infrared spectroscopy (IR) techniques were used to investigate the compatibility between prednicarbate and several excipients commonly used in semi solid pharmaceutical form. The thermoanalytical studies of 1:1 (m/m) drug/excipient physical mixtures showed that the beginning of the first thermal decomposition stage of the prednicarbate (Tonset value) was decreased in the presence of stearyl alcohol and glyceryl stearate compared to the drug alone. For the binary mixture of drug/sodium pirrolidone carboxilate the first thermal decomposition stage was not changed, however the DTG peak temperature (Tpeak DTG) decreased. The comparison of the IR spectra of the drug, the physical mixtures and of the thermally treated samples confirmed the thermal decomposition of prednicarbate. By the comparison of the thermal profiles of 1:1 prednicarbate:excipients mixtures (methylparaben, propylparaben, carbomer 940, acrylate crosspolymer, lactic acid, light liquid paraffin, isopropyl palmitate, myristyl lactate and cetyl alcohol) no interaction was observed.