Semisolid Dosage Forms Research Articles

Antifungal Cream Preparation of Galangal Rhizome Extract (Alpinia galanga L.)

Cream is a semi-solid emulsion dosage form of both water-in-oil (W/O) or oil in water (O/W) type containing one or more dissolved or dispersed ingredients in the corresponding base material (containing no less than 60% water). Cream is usually used as emollient or containing active pharmaceutical ingredients on the skin (Ansel, 2008). The advantage of cream are the application practicallity, water washeability, and the easiness to spread evenly. In this research, we formulated cream containing rhizome Galangal rhizome. According to Darmono (2008), Galangal rhizome has various properties such as antifungal and antibacterial activities. Galangal rhizome contains 1-asetoksikhavikol asetat (ACA). ACA is an antifungal. ACA has good solubility in 70% ethanol. We maserated Galangal rhizome (Alpinia galangal L.) to extract ACA from the simplicia. As for the cream base, we use hidrophilic base containing emulgators stearic acid and triethanolamine, with glycerin as humectant. During the optimization, we chose three formulas, formula 1 (10% stearic acid , 2% triethanolamin, 5% glycerin, and 0.01% vitamin E), formula 2 (15% stearic acid , 3% triethanolamin, 10% glycerin, and 0.05% vitamin E), and formula 3 (20% stearic acid, 4% triethanolamin, 7.5% glycerin, and 0.09% vitamin E). We used the bases to contain 10% of the extract. The results show that formula 1, formula 2, and formula 3 had typical smell of Galangal rhizome, brown color, and thick consistency. All formulas are homogenous. Formula 1 the best stability. We conclude that Galangal rhizome (Alpinia galanga L.) can be formulated in cream form with our formula 1 had the best stability among others.

QbD guided early pharmaceutical development study: Production of lipid nanoparticles by high pressure homogenization for skin cancer treatment

This research attempts to bring together the positive aspects of lipid nanoparticles and Quality by Design (QbD) approach for developing a novel drug delivery system for skin cancers and aktinic keratosis. Lipid nanoparticles which is one of the most efficacious options for topical treatment of skin diseases were prepared due to their ability to overcome the complex structure of skin barrier and to enhance the skin penetration. Since the formulation development contains complex variables of active ingredients, raw materials or production method; all the variables of the product should be elaborated. QbD approach which refers to design and develop formulations and manufacturing processes to maintain the prescribed product quality was also successfully adopted to achieve a time- and cost-saving process ensuring a high-quality product.5-Fluorouracil (5-FU) loaded lipid nanoparticles, both solid lipid nanoparticles and nanostructured lipid carriers, were developed and characterized by following QbD steps. Optimal lipid nanoparticle formulation with guaranteed quality which was within the design space has been reached through the artificial neural networks. The optimal lipid nanoparticle formulation which is a NLC formulation with a mean particle size of 205,8 ± 9,34 nm, narrow size distribution (0.279 ± 0.01) and negative zeta potantial −30,20 ± 0,92 was produced by high pressure homogenization method. Cytotoxicity profiles of the optimal NLC was determined by cell culture studies on epidermoid carcinoma cells and human keratinocyte cells. Optimal NLC showed significantly higher anticancer effect on epidermoid carcinoma cells than free 5-FU and also less cytotoxicity towards human keratinocyte cells. Optimal NLC was formulated in hydrogel formulation for ease of application which has suitable occlusive and mechanical properties, viscocity and pH for patient complience. The cumulative amount of 5-FU in dermal tissues of rat skin was found 20.11 ± 2.14 μg/cm2 and 9.73 ± 0.87 μg/cm2 after application of NLC enriched hydrogel and 5-FU hydrogel respectively.In conclusion, this study showed that a time and cost saving process ensuring a high-quality product can be obtained by QbD guided formulation development study with the help of artificial neural networks. A novel semisolid dosage form enriched by NLC which is promising for topical treatment of skin cancers was developed.

Study of excipients influence on the cranberry oil releasing from the rectal suppository

Cranberry oil is a sufficiently perspective compound for using in the semisolid rectal dosage forms because it possesses regenerating, antioxidative, anti-inflammatory actions together with practical toxicity absence. The aim of this work is the study of influence of the excipients, which are used in suppository manufacturing (delivery bases and surfactants) on the biopharmaceutical characteristics of the rectal dosage form with cranberry oil. Materials and methods . Concentration of surfactants in all rests was 2 % from the suppository mass, cranberry oil contain was 0.25 g in each suppository taking into account data of the advance investigations. Study was carried out according to plan of single-factor analysis of variance with repeated observations. Releasing of cranberry oil from the suppositories was chosen as a parameter of optimization for the first step of biopharmaceutical availability study. The study was carried out by equilibrium dialysis method by Kruvchinsky at the temperature 37.0 ± 0.5 oС through the semipermeable film “Kuprofan”. After 30 minutes the antioxidative activity was set on the model of non-fermentative initiation of the free radical oxygenation in all dialysates. Results . According to the presented data factor A (sort of base) and factor B (sort of surfactant) make significant influence on cranberry oil releasing from the suppositories (F exp. >F tabl ). At the same time influence of the surfactants sort is slightly more significant than for the base. Also, interaction between these factors was statistically significant. On the base of obtained data, the range of influence of studied factors on the intensity of releasing of cranberry oil bioactive substances from suppository formulation was arranged: В > А > A x B. Conclusions. Variance analysis of results revealed that formulation with confectionary solid butter and emulsifier №1 provide optimal releasing of cranberry oil from the suppositories.

Nanoemulsion for skin drug delivery

The use of nanoemulsion in augmenting dermal and transdermal effectiveness of drugs has now well established. The development of nanoemulsion based semisolid dosage forms is an active area of present research. However, thickening or liquid-to-semisolid conversion of the nanoemulsions provides opportunities to the formulation scientist to explore novel means of solving instability issues during transformation. Extending knowledge about the explicit role of nature/magnitude of zeta potential, types of emulsifiers and selection of appropriate semisolid bases could place these versatile carriers from laboratory to industrial scale. Nanoemulsions are termed as biphasic (O/W or W/O) or multiple nanoemulsions (W/O/W). Oil phase components include fatty acids (e.g., oleic acid), esters of fatty acids and alcohols (e.g., isopropyl myristate, isopropyl palmitate, ethyl oleate), medium chain triglycerides, triacetin, terpenes (e.g., limonene, menthol, cineole) and other penetration enhancers. Till date several approaches have been employed to develop nanoemulsions (size range 20–200 nm) which are High-energy emulsification and Low-energy emulsification. NanoemulsionS are found effective to treat psoriasis, dermatitis and cancer.

A study on awareness regarding disposal of unused medicines among consumers at a tertiary care teaching hospital of north india

Background: In the recent years, large number of human pharmaceuticals have been introduced to the environment by landfill when household medications are thrown to trash and liquid medications gain access to the environment via liquid drainage systems. There is lack of knowledge and awareness in the general public regarding the safe disposal of unused and expired medicines. The objective was to assess the awareness regarding disposal of unused medicines among consumers at a tertiary care teaching hospital of north IndiaMethods: It was a cross-sectional observational questionnaire-based study carried out on 220 consumers in medicine outpatient department (OPD) of a tertiary care teaching hospital in North India for 3 months. All the participants were provided the pre-validated self-administered questionnaire. The final questionnaire consisted of twelve questions to assess participants’ knowledge and attitude towards disposal of the medicines. The data was analyzed with the help of descriptive statistics.Results: It is quite evident from the present study that majority of participants 56.36% stated 1-5 drugs were left-over drugs at their homes. Most of the leftover medicines were analgesics in 59.1% followed by antibiotics in 51.36%. Most common dosage form of these leftover medicines were tablets in 85.9% of respondents. Majority of the respondents (55.9%) were not aware of the adverse outcomes of the pharmaceuticals in the environment. The most common method followed by majority of the participants for disposing of the solid, semi-solid and liquid dosage forms was garbage in 95%, 91.4% and 76.4% of consumers respectively. About 9.31% of the participants were in favour of initiating a program to collect unused medications from home.Conclusions: It can be concluded from the present study that the consumers had poor knowledge regarding the safe drug disposal techniques. Therefore, efforts need to be done by the health care professionals to make people educate regarding the safe drug disposal techniques.

Comparative study of antimicrobial activity of composite semisolid dosage forms for differentiated therapy of foot mycosis

The aim of work is the study of antimicrobial activity of composite semisolid dosage forms for differentiated therapy of foot mycosis with 2-mercaptobenzthiazol and chinozol, namely the paste on emulsive base and the ointment on hydrophilic delivery vehicle. Materials and methods . As the objects of investigation, the paste on emulsive base and the ointment on methylcellulose glycerogel, providing optimal releasing of 2-mercaptobenzthiazol and chinozol from the delivery vehicle and also appropriate semisolid dosage forms (placebo) were used. Antimicrobial activity of paste for nails, ointment for external use and their delivery vehicle was determined for Candida albicans fungi by diffusion into agar method. Candida albicans fungi take second place by the frequency of foot mycosis occurrence after dermatophytes and gram-positive ( Staphylococcus aureus ), gram-negaitive ( Pseudomonas aeruginosa ) pathogenic bacteria because of high frequency of mixtinfection joining the foot mycosis. As the references the well-known antimycotic medications which are registered in Ukraine and for enough time have been used in practice of foot mycosis therapy – cream “Clotrimazole 1 %” (Salutas Pharma, Germany), cream “Exoderil 1 %” (GlaxoSmithKline Pharmaceuticals S.A., Poland), ointment “Kanespor 1 %” (Kern Pharma S.L., Spain) were used. Results . It was revealed that investigated pharmacotherapeutic medicines are characterized by high efficacy for above mentioned microflora. Bases of experimental dosage form have a moderate antimycotic and antibacterial activity caused by onycholytics (salicylic and benzoic acids) and keratolytic (carbamide) presence in formulations. In comparative microbiological studies it was established that the experimental paste for onychomycosis therapy, which contains the composition of nonspecific antimycotics and onycholytics, noticeably surpasses one of the most effective medications – ointment “Kanespor” by the area of growth inhibition zone for pathogenic fungi Candida albicans and gram-negaitive bacteria Escherichia coli and Pseudomonas aeruginosa . It was revealed that by the diameter of growth inhibition zone for above mentioned microorganisms the developed ointment surpasses such modern remedies as cream “Clotrimazole 1 %” and cream “Exoderil 1 %”, which are widely used in topical treatment of dermatological mycosis. Conclusions . Obtained results of antimicrobial activity study of composite semisolid dosage forms for differentiated therapy of foot mycosis on the base of combination of 2-mercaptobenzthiazol and chinozol allow to predict their high clinical value and possibility of providing the domestic dermatology with affordable and effective pharmacotherapeutic medicines, creating the real alternative to import products.

Physicochemical characterization and thermal behavior of hexosomes containing ketoconazole as potential topical antifungal delivery system

Objective: The main purpose of this article is to show the valuable characteristics that liotropic liquid crystal systems possess to be employed as new drug delivery systems.Significance: Colloidal aqueous dispersions of lyotropic liquid crystal mesophases such as the identified as cubosomes and hexosomes, and so on, have received considerable attention due to their unique nanostructures and their thermodynamic properties, which provide the potential as a sustained drug release matrix. Additionally, their large surface area and similarity with the liquid crystal structures of intercellular lipids of stratum corneum enhances the interaction with the skin and mucous, increasing the potential for topical drug delivery efficiency of biopharmaceutical class II drugs as the antifungal ketoconazole.Methods: This article presents the results in morphological characteristics, particle size, ζ potential, flow, thermal behavior and drug release studies of hexosomes containing ketoconazole (LHLC-K) obtained with glycerol monooleate, propylene glycol monolaurate, poloxamer, and water mixtures.Results: This colloidal system exhibits a Newtonian-type flow and a hexagonal nanostructure with a median particle size of 107 ± 20 nm and ζ potential of +4.45 ± 0.50 mV. Through differential scanning calorimetry studies, the LHLC-K demonstrated physical and chemical stability for more than six months and mesophasic thermal reversibility between 10 and 50 °C. Finally, LHLC-K releases ketoconazole following a kinetics described by the first order model.Conclusions: Physicochemical properties of the hexosomes containing ketoconazole are important for topical mycosis treatment administration, conditions of storage, and for its incorporation into the formulation of semi-solid dosage forms.

Greenness assessment as per Eco-scale and AMVI metrics for the chromatographic assay of selected drugs in a semisolid dosage form and in tissues

A simple green sample preparation procedure and RP-HPLC method were developed and validated for the determination and quantification of two anti-hemorrhoid drugs in semisolid dosage form as well as in rat rectal tissues. Sample cleanup was performed using solid-phase extraction on strata-X prefilled (100 mg, particle size 33 µm, 3 ml) cartridges; conditions were optimized to obtain maximum recoveries and minimal baseline noise. Separation was carried out on Xselect C18 column (250 × 4.6 mm id, 5 µm particle size), a mobile phase consisting of ethanol: 0.01% aqueous sodium carbonate solution (75:25 by volume) at a flow rate of 1 ml/min and UV detection at 220 nm. The method was validated as per the ICH guidelines and FDA guidance for bioanalytical method validation. Greenness of the method was assessed throughout the whole procedure of sample preparation, separation and quantification using Eco-scale and analytical method volume intensity metrics and was found to be environmentally friendly as it was also manifested by its greenness profile. The developed method was found to be suitable for the determination of the selected drugs in their marketed formulation as well as in biological samples. Being simple and eco-friendly technique, it can be used for routine analysis in quality control laboratories.

A new design for the review and appraisal of semi-solid dosage forms: Semi-solid Control Diagram (SSCD).

The Semi-solid Control Diagram (SSCD) is a new tool designed for the study of different excipients and different semi-solid dosage forms. It can be used to review and evaluate different formulations and/or batches and facilitate the selection of one of them that will present the most suitable galenic characteristics for topical application. It is also useful to track stability studies by comparing the diagrams, which allows to measure the impact of subjecting the formulation to different conditions and times to be examined. In this study, the Semi-solid Control Diagram (SSCD) is used as an instrument for studying and evaluating semi-solid pharmaceutical dosage forms, by comparing several different semisolid preparations (lipogels). With these results, the tool is validated and the best formulation has been discriminated from the others.

Taxifolin: Evaluation Through Ex vivo Permeations on Human Skin and Porcine Vaginal Mucosa.

Taxifolin (TAX) is a flavonoid that has numerous pharmacological properties, including an antioxidant ability superior to that of other flavonoids due to its particular structure. Nevertheless, it has low oral bioavailability, which limits its therapeutic application. In this context, potentially important approaches for systemic drug delivery could be by alternative routes such as skin and vaginal mucosa, once both routes have a variety of advantages compared with the oral route, including the ability to bypass both first-pass hepatic metabolism and the consequent degradation in the gastrointestinal tract. Vaginal delivery could also account for a local effect, or an effect on circumvent microregion. The major objective of this study was to develop and validate a high-performance liquid chromatography (HPLC) method for the determination of TAX in a semisolid dosage forms and then to evaluate ex vivo permeations across porcine vaginal mucosa and human skin. TAX was incorporated into an oil-in-water emulsion developed previously by our group. Method for quantification was developed and validated using HPLC. Permeation through human skin and vaginal porcine mucosa were conducted in Franz-type cells. The method was precise (CV < 5%), accurate (recovery between 98% and 102%), linear (R2> 0.99), specific, and robust. Permeation experiments through porcine vaginal mucosa and human skin presented permeated percentages equal to 87.43% and 48.09% (per dose), respectively. The results suggest that, in the matrixes studied, TAX may be able to exert its biological activities systemically when applied by these routes. Furthermore, it exhibits greater permeability potential when administered by intravaginal route.

Basis of optimal concentration of active pharmaceutical ingredients in combdrugs for external use with antimycotic activity

An analysis of the state of modern resources for pharmacotherapy of foot mycosis was carried out. It showed that the creation of semisolid dosage forms for the topical skin, foot web space and nail treatment with bioactive compound from the group of nonspecific antimycotic substances (2-mercaptobenztiazol, chinozol) on the base of domestic technology ia actual for the modern pharmaceutical and medical science. Successful realization this project will allow to propose the effective complaentic and available for the wide segment of the Ukrainian medications for the effective foot mycisis therapy to the domestic dermatology and will make a real alternative imported pharmacotherapeutical preparations.&#x0D; The aim of this work is a scientifically basis of 2-mercaptobenztiazol and chinozol concentration in ointment’s compositions for the foot mycosis therapy.&#x0D; Investigations of efficacy of model compositions on the sodium carboxymethylcellulose glycerogel base with combination of mebetizol and chinozol in concentration from 0 to 10% were carried out by the two-layer agar plate method against Candida albicans АТСС 885-653 according methematic model of two-factor experiment.&#x0D; It was ascertained that combining 2-mercaptobenztiazol and chinozol in semisolid dosage forms for external use allows to predict the potentiation of their action in mycosis topical therapy. At the same time both active pharmaceutical ingredients concentration makes a sighnificant influence on the antimycotic activity of experimental compositions. It was ascertained that chinozol concentration makes the greatest influence on the antimycotic activity of ointment compositions. At the same time 2-mercaptobenztiazol concentration and active pharmaceutical ingredients joint use in dosage form also make a statistically significant influence on the antimycotic activity level of semisolid dosage forms. Variance analysis of investigation’s results showed that combining 10% 2-mercaptobenztiazol and 10% chinozol provides with optimal level of ointments specific activity. That fact allows to predict the advisability of making pastes on the base of these and active pharmaceutical ingredients combination in semisolid dosage forms for foot onychomycosis therapy.&#x0D; Results of antimycotic activity of ointments containing combinations of lower concentration of studied nonspecific antimycotic substances allow to propose them for the therapy of foot and interdigital space mycotic affections.

Study of influence of the surface-active substances concentration on releasing of praziquantel from the rectal suppository

Acne dermatosis (rosacea, perioral dermatitis, seborrheic dermatitis etc.) are one of the most actual problem in dermatology. Praziquantel is an antiparasitic medication effective towards trematodes, cestodes. Investigations developed by domestic scientists revealed antidemodicosis activity of praziquantel. Use of semisolid dosage forms for rectal administration will allow to increase its efficacy and minimize the risks of adverse reactions.&#x0D; On the department of technology of medications Zaporizhzhia State Medical University research of development of praziquantel rectal dosage form for therapy of acne dermatosis, complicated with demodicosis, and its technology is carried out. As a result of biopharmaceutical investigations it was determined that combination of excipients – the base (confectionary fat 60%, 10% paraffin, 30% cocoa butter) and surfactant (distilled monoglycerides) provides with the optimal praziquantel releasing.&#x0D; The aim of this work is study of excipient using in manufacturing of suppository (bases and surfactants) influence on the biopharmaceutical characteristics of praziquantel rectal dosage form.&#x0D; Investigation was carried out by the one-factors dispersive analysis with repeated observations By way of a parameter of optimization praziquantel releasing was chosen as the first step of bioavailability investigation. Praziquantel releasing from suppository was studied by the equilibrium dialysis by Kruvchinsky’s method at temperature 37 ± 0,5 °С through a cellophane semipermeable membrane «Kuprofan» film using Franz diffusion cell apparatus. Ethyl alcohol was chosen as a dialysis medium considering the solubility of praziquantel. Concentration of released praziquantel after 30 minutes of the dialysis was determined by spectrophotometric analysis.&#x0D; As a result of biopharmaceutical investigation of praziquantel suppositories it was determined that surface-active substances (distilled monoglycerides) concentration has a statistically significant influence on its releasing from rectal dosage form. It was ascertained that 0,5% concentration of distilled monoglycerides provides with the optimal releasing of praziquantel from rectal suppositories.

SOFT CHEWABLE DRUG DELIVERY SYSTEM: ORAL MEDICATED JELLY AND SOFT CHEW

Oral route is most commonly used for administration of medicament since they are economical, easy to administer, & high patient acceptance. Due to difficulty in administration of therapeutic agents to dysphagia patients it becomes necessary to develop a formulation in order to overcome such inconvenience. Jellies are semisolid dosage form they are transparent, non greasy, & can be used internally as well as externally. Its matrix include large amount of water & they resemble to mucilage but possess jelly like consistency. Advantages of chewable formulation are that it does not require water for ingestion, aesthetic appearance, and good texture. Soft chew is solid, single dose formulation. It is used as acute medication since it is mobile drug delivery systems. They are formulated using heating & congealing technique. It serves as novel dosage form with wide applications in pharmaceuticals, nutraceuticals and over the counter medicines Keywords: Jellies, Soft chew, Nutraceuticals

Study of bases influence on the biopharmaceutical characteristics of the pastes for onychomycosis therapy

According to the European and American authors the onychomycosis prevalence in the world has amount from 8.0 % to 26.9 %. Topical treatment of onychomycosis in most cases is the only acceptable method of therapy mainly due to high safety. Etiotropic topical pharmacotherapy of this pathology is carried out by the dermatomicotic medicines – creams, ointments, gels, solutions. Nail polishes are the specific dosage forms for onychomycosis therapy. However antimycotic polish therapy is sufficiently effective only in case of treatment the surface white and distal-lateral form of onychomycosis, but just in case when less than 1/3 of nail plate is affected. Also wide application is limited to length of use (from 6 month to 1 year) and high therapy cost. According to above mentioned information, development of specific semisolid dosage form for onychomycosis therapy without removing the nail plate and allowing combination high efficacy of medical substances even in case of nail-bed affection, rational term of treatment and economical availability is rational. Presence of these effects may be reached by the way of combination in semisolid dosage form for appliication on the nail plate – the paste – substances with keratolytic and antimycotic action. At the same time use of acid combination as a keratolytic for pH decreasing in tissue of the nail plate and fungi growth inhibition and also providing with penetration of active components of paste for onychomycosis therapy. As a result of this development of semisolid dosage form for the topical treatment of onychomycosis with biologically active substances from the group of nonspecific antimycotics (2-mercaptobenzthiazol, chinozol) with broad spectrum of antimycotic, antibacterial activity and safety has a scientific and practical interest. The aim of this work is biopharmaceutical substantiation of optimal base for semisolid dosage form – paste for etiotropic therapy of onychomycosis. Materials and methods. As a device for developing pharmacotherapeutical preparation hydrofobic and emulsion bases resistant to combination with sufficiently aggressive keratolytics and described in literature were studied. As an active pharmaceutical ingredient for antimycotic paste 2-mercaptobenzthiazol and chinozol in concentration 10% and 10% accordingly for providing with the optimal level of antifungal activity were used. As keratolytic substances traditionally used for onycholysis: carbamide, mixture of salicylic and benzoic acids in concentration described in literature were used. At the same time chinozol shows keratolytic effect and in that capacity is used in formulations of chinozolo-salicylic, chinozolo-dimexidic and also carbamidic plasters for nails. The content of dry substances and plasticizers in formulations of onycholytic pastes was chosen taking into account the requirements of Ukrainian Pharmacopoea and normative document for this dosage form. Taking into account the advisability of high dispersion degree of medical substances in semisolid dosage forms for external use and physical-chemical properties of 2-mercaptobenzthiazol the latter was added in emulsion bases after preliminary dissolution in polyethylenoxyde 400 with heating. Keratolytics were added as a suspension in all bases. Investigations of scientifically substantiation of the base of paste for onychomycosis therapy were carried out according to plan of single-factor analysis of variance with repeated observations. For all selected compositions the releasing of active pharmaceutical ingredients (2-mercaptobenzthiazol and chinozol) from ointments were studied with equilibrium dialysis method by Kruvchinsky at the temperature 25.0 ± 0.5 °С (temperature on the surface of nail) through the semipermeable film “Kuprofan” in the Franz diffusion cell apparatus (producer PermeGear, Inc., USA). As a dialysis medium taking into account 2-mercaptobenzthiazol solubility was used solution containing methanol and water 1:1 and chinozol releasing was carried out into water. Concentration of active pharmaceutical substances released from experimental pastes after 2 hours was determined spectrophotometrically. Results . Carried out verification of average results of 2-mercaptobenzthiazol and chinozol releasing by the Dunkan’s multiple rank test allowed to build the preferred series of pastes base influence on the intensity of active pharmaceutical ingredients releasing. Obtained results showed the sighnificant advantage of the emulsion ointment base providing with optimal level of 2-mercaptobenzthiazol and chinozol releasing from experimental compositions of semisolid dosge forms for onychomycosis therapy. Conclusions . It was determined that sort of the base makes a sighnificant influence on 2-mercaptobenzthiazol and chinozol releasing from the antimycotic pastes for onychomycosis therapy. Variance analysis of results revealed that emulsion vehicle containing acid-resisting emulsifier provides with optimal 2-mercaptobenzthiazol and chinozol releasing.

Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases.

Study of base influence on the active pharmaceutical ingredients releasing from combined ointments with antimycotic action

Questions of mycotic diseases therapy keep staying in focus of clinical dermatology interest that is caused first of all by their considerable prevalence for international population. At the same time the dominating pathologies in this area are foot mycosis including skin, foot web space and nail plate affections. Etiotropic pharmacotherapy of foot skin and web spaces is carried out using topical antifungal medications effective against dermatomycetes. Also taking into account the frequent mixt infections, medicines with antibacterial action are desirable. Also topical antifungal medicines for therapy of foot skin mycosis have to satisfy the next requirements as rapid absorbance, safety and usability besides efficacy. Domestic dermatology for these aims has a great pharmacotherapeutical arsenal proposed by 34 semisolid dosage forms, 15 from them are made in Ukraine and the remainder are imported in our country. At the heart of practically all antimycotic medicines for topical therapy of smooth foot skin (as imported so domestic) imidazole and triazole derivatives are used and because of their high value they limit the therapeutical potential of population with low profit. 2-mercaptobenzothiazole is interesting as biologically active component of ointments not only because of broad spectrum of antifungal and antibacterial action but also exceptional hydrophobic characteristics which provide long adhesion even after washing during hygienic procedures. In this connection creating of semisolid dosage forms for the topical treatment of skin integument and interdigital folds with biologically active substances from the group of nonspecific antifungal matters (2-mercaptobenzothiazole, chinosolum) on the base of domestic technologies is actual for modern pharmaceutical and medical science. During creating of semisolid dosage forms for the external use one of the main experimental fragments is a selection of base which provides high consumer characteristics of medicine and its efficacy. The aim of this work is biopharmaceutical validation of rational composition of semisolid dosage form for external use containing the combination of 2-mercaptobenzothiazole and chinosolum. Materials and methods. As a delivery vehicle for developing pharmacotherapeutical medicine the bases widely used in manufacturing of semisolid dosage forms, providing easy “wipe-off effect after application, non-allergic and non-sensibilic after tracing, available for national producer and described in literature were studied. As the active pharmaceutical ingredients for antimycotic ointment 2-mercaptobenzothiazole and chinosolum in concentration 1% and 1% accordingly providing with suitable level of antifungal activity were used. Taking into account the advisability of high dispersion degree of medical substances in semisolid dosage forms for external use and physical-chemical properties of active pharmaceutical ingredients 2-mercaptobenzothiazole was added in all bases after preliminary dissolution in polyethylenoxyde 400 with heating and chinosolum was added after dissolution in prescribed or minimal amount of water. 2-mercaptobenzothiazole and chinosolum releasing from ointment compositions was studied with equilibrium dialysis method by Kruvchinsky at the temperature 32±0,5˚С through the semipermeable film “Kuprofan” in the Franz cell apparatus (producer PermeGear, Inc., USA). As a dialysis medium taking into account 2-mercaptobenzothiazole solubility we used solution containing methanol and water 1:1 and chinosolum releasing was carried out into water. Concentration of active pharmaceutical substances released from experimental ointments after 30 min was determined by spectrophotometric method. Results . The obtained results indicate significant advantage of the hydrophilic ointment bases, which provide an optimal level of release of 2-mercaptobenzothiazole and chinosolum from the experimental composite soft dosage forms for external use. Based on the obtained data, ointment compositions with 2-mercaptobenzothiazole and chinosolum on the basis of sodium carboxymethylcellulose (prescription №1) and methylcellulose (prescription №2) glycerogel were selected for further research. Conclusions. It was established that the sort of base significantly influences on 2-mercaptobenzothiazole and chinosolum releasing from the antimycotic formulations of semisolid dosage forms for external use. Variance analysis of results revealed that delivery vehicles on the base of sodium carboxymethylcellulose and methylcellulose glycerogel provide optimal 2-mercaptobenzothiazole and chinosolum releasing.

The study of excipients’ influence on Clopidogrel releasing from the rectal suppositories

Сердечно-сосудистая патология – ишемическая болезнь сердца и мозга, окклюзивные заболевания периферических артерий – наиболее частая причина заболеваемости, смертности и инвалидности населения мира. В основе всех этих заболеваний лежит единый патологический процесс – атеросклероз. Его клиническим проявлением является атеротромбоз, вызывающий подавляющее большинство острых поражений коронарных, мозговых и периферических артерий. Развитие тромбоза в сердечно-сосудистой системе – многофакторный процесс, при этом важная роль отводится активации тромбоцитов, что является основанием для клинического использования антитромбоцитарных препаратов для первичной и вторичной профилактики тромботических осложнений. Тесная взаимосвязь атерогенеза и тромбообразования патогенетически обосновывает назначение атеротромботических препаратов как с лечебной целью, так и для первичной и вторичной профилактики. На протяжении последних лет ведущее место среди препаратов с механизмом тромбоцитарной антиагрегации занимает клопидогрель. Он относится к фармакологической группе антагонистов аденозиновых рецепторов, подавляющих активацию тромбоцитов путем селективного связывания АДФ со специфическими рецепторами. Помимо этого, клопидогрель обладает мощным поливалентным антиагрегантным эффектом на тромбоциты. Также применение клопидогреля приводит к достоверному снижению уровня триглицеридов и оптимизации других показателей липидограммы. На фармацевтическом рынке Украины в настоящее время клопидогрель представлен в форме таблеток, покрытых оболочкой, отечественного и импортного происхождения. Альтернативой пероральному использованию клопидогреля является ректальный путь его введения, позволяющий за счет повышения биодоступности лекарственного вещества понизить дозу активного фармацевтического ингредиента и минимизировать риски возникновения нежелательных побочных реакций со стороны организма пациента. Цель работы – изучение влияния вспомогательных веществ, использующихся в технологии изготовления суппозиториев (основ-носителей и поверхностно-активных веществ), на биофармацевтические свойства ректальной лекарственной формы клопидогреля. Материалы и методы. В качестве носителей для ректальной лекарственной формы клопидогреля исследовали суппозиторные основы и поверхностно-активные вещества, широко применяемые в промышленном и аптечном производстве мягких лекарственных форм и описанные в специализированной литературе. Суппозитории готовили методом выливания, концентрация поверхностно-активных веществ во всех опытах составляла 2 % от массы суппозиториев, содержание клопидогреля – 0,075 г в каждом суппозитории. Исследование проводили по плану двухфакторного дисперсионного анализа с повторными наблюдениями. При изготовлении суппозиториев клопидогрель вводили в их состав по типу суспензии, тщательно измельчая лекарственное вещество с равным количеством спирта этилового, затем с частью основы и дальнейшим добавлением полученной смеси ко всей расплавленной основе. В качестве параметра оптимизации избрали высвобождение клопидогреля как первый этап определения биологической доступности. Высвобождение клопидогреля из суппозиториев изучали методом равновесного диализа по Крувчиньскому при температуре 37,0 ± 0,5 °С через целлофановую полупроницаемую мембрану-пленку «Купрофан» по ГОСТу 7730 на девятипозиционной станции с диффузионными ячейками Franz Cells (производитель PermeGear Inc., США). Диализной средой с учетом растворимости клопидогреля выбран спирт этиловый. Концентрацию высвободившегося через 30 минут клопидогреля устанавливали спектрофотометрически. Результаты . Установлено, что вид основы-носителя и вид поверхностно-активных веществ оказывают значимое влияние на высвобождение клопидогреля из ректальных суппозиториев. Выводы. Наибольшее влияние на высвобождение клопидогреля из суппозиториев ректальных оказывает вид основы-носителя. Дисперсионный анализ результатов исследований показал, что оптимальное высвобождение клопидогреля из суппозиториев ректальных обеспечивает композиция полиэтиленоксидной основы и твина-80.

FORMULASI KRIM EKSTRAK KULIT PISANG AGUNG SEMERU DAN PISANG MAS KIRANA VARIETAS LUMAJANG

Banan peel of Agung Semeru and banana peel of Mas Kirana, is one part of banana fruit containing antimicrobial compounds that contain phytochemical components. The purpose of this research is to know the quality of cream from banana peel extract of Agung Semeru, Mas Kirana and combination of both using 100% concentration (the best concentration, based on previous research results). In the test the cream is done organoleptic test, test homogeneity, spreading test, pH test and absorption test. The results obtained on the organoleptic test seen from the color of brown cream, semi-solid dosage form, and the smell of banana skin cream typical test homogeneity does not occur agglomeration, pH ranges from 5-6 and still safe for the skin, has a cream that meets the requirements of absorption that is more 1 mg / 1 ml. A / M cream scattering test is easy to be applied so that the extract cream of skin extract of Agung Semeru banana skin extract, Mas Kirana and combination fulfill the scatter test.

Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice.

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems).

Influence of solubilizer PEG-40 hydrogenated castor oil on carbopol gels’ structural-mechanical properties

Rheological properties affect all stages of the drug development – from development to production, the characteristics of the final products and stability.A lot of substances have complex rheological properties; their viscosity and elasticity can vary depending on conditions acting from the outside, such as stress, deformation, time factor and temperature. Concentration, stability and composition also significantly affect the rheological properties of drugs.One of the current trends in modern pharmacy is the development of drugs in the form of gels. The rheological properties of gels are significantly influenced by surface-active substances, stabilizers, solubilizers, stabilizing their structure.A special group of stabilizers are hydrogenated vegetable oils and their compounds with polymers, which have the ability to structure formation in interphase layers and in the volume of phases. For this purpose, PEG-40 hydrogenated castor oil is widely used.The aim of this work is to study the effect of hydrogenated castor oil, used as an emulsifier, solubilizer, viscosity modifier and solvent in the technology of semisolid dosage forms, on the structural and mechanical properties of carbopol gels.Materials and methods. 1% gel carbopol with additives PEG-40 hydrogenated castor oil in the concentration range from 1 to 5 % was investigated as experimental samples of the gel base. A 10 % propylene glycol additive was used as humectant and plasticizer.Structural and mechanical studies were carried out using a rotational viscometer «RheolabQC», Anton Paar (Austria) with coaxial cylinders CCC27/SS. The graphs of the gels were automatically plotted using the computer program.Results. Analysis of the rheological parameters of the carbopol with PEG-40 hydrogenated castor oil gel base shows that the solubilizer has an active influence on the structural and mechanical properties of the base.Addition of PEG-40 GMM to the carbopol gel increases the yield strength by 53 % (to 188.22 Pa at 5 % PEG-40 GKM injection), reduces the value of the yield strength of the base to 337.0–374.0 Pa s and, accordingly, increases the structure breakdown from 1.56 Up to 2.39 Pa s with an increase in the shear rate to 350 s-1, increases the hysteresis loop to 22525.9 Pa/s while reducing the stability of the system by more than 2 times and increases the value of mechanical stability to 1.16–1.37, that at the end can affect the deterioration of the restoration of the structure after deformation.Conclusions. Was studied the effect of the solubilizer PEG-40 hydrogenated castor oil on the structural and mechanical properties of carbopol gels using the «RheolabQC», Anton Paar rotary viscometer. It has been found that the use of this solubilizer in excess of 5 % is impractical due to the deterioration of the rheological properties of the gel, a decrease in mechanical stability and a decrease in the consumer qualities of the drug.