[Formulation and in vitro examination of furosemide-containing suppositories and preliminary experiences of their clinical use]. / Furosemid-tartalmú kúpok elóállítása, in vitro vizsgálata és a preklinikai alkalmazás tapasztalatai.

Rectal suppositories containing Furosemide (4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid) and Furosemide Sodium were formulated with various suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be the best from among the vehicles having various physical-chemical properties. The diuretic effect of the two suppositories was compared in a prospective, cross-over clinical trial including 8 patients. Both preparations have induced and increase of urine flow, which was comparable to the diuretic effect of the tablet. Thus the possibility of rectal use has been added to the modalities of therapeutic Furosemide administration.

Formulation and in vitro examination of furosemide containing suppositories and preliminary experiences of their clinical use.

Rectal suppositories containing furosemide (4-chloro-N-furfuryl-5-sulfamoylanthranilic acid) and furosemide sodium were formulated with various suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be the best from the vehicle having various physical-chemical properties. The diuretic effect of the two suppositories was compared in a prospective, crossover clinical trial including 8 patients. Both preparations have induced an increase of urine flow, which was comparable to the diuretic effect of the tablet.

Formulation and in vitro study of antibacterial vaginal suppositories.

Vaginal suppositories frequently used in gynaecological therapy were studied. Several antibacterial pharmacons are used for the topical treatment of vaginitis of various origins. In view of the fact that the liberation of the given active substance and the subsequent therapeutic effect may be improved or inhibited by the vehicle, our aim was to find the optimal suppository base for vaginal suppositories containing sulfadimidine, chloramphenicol and gentamicin sulfate by means of in vitro experiments. On the basis of breaking hardness, disintegration time and spreading properties the French Suppocire NA product, and compositions of macrogols with lower molecular weight proved to be the best lipophilic and hydrophilic bases, respectively. Among the lipophilic bases the in vitro drug liberation of Suppocire NA was significantly better (P < 0.05) than the other lipophilic bases. This vehicle is recommended for the topical treatment of vaginitis, as these suppositories have the further advantage that they can easily be produced on a magistral, galenical or industrial scale as well.

Formulation of diazepam containing rectal suppositories and experiences of their biopharmaceutical study.

Methodology and the results of the in vitro membrane diffusion and in vivo bioavailability studies are presented. The results confirm a correlation between in vitro and in vivo findings. Hydrophilic macrogol-mixture with great molecular mass can be recommended as the optimal vehicle for formulation of diazepam suppositories.

[Deformation of tablets according to breaking hardness]. / Tabletták deformációjának tanulmányozása nyomási szilárdságvizsgálat alapján.

The authors were the first to test the breaking process of tablets in home respect. In experiments on the breaking of tablets a tablet hardness tester developed by the Chemical and Pharmaceutical Works Ltd. Chinoin (Budapest) was used. With an appropriate program, this permitted not only a qualitative evaluation of the breaking curves (Fig. 2-4.) also an assessment of the breaking work relating to the breaking strength and even the work needed for various deformation processes (Tab. I-II.). The concept of the breaking factor was introduced: this allows a differentiation of tablets even if the breaking strengths are the same (see Tab. III. 1-2 tablets; with two samples analysis; p < 0.05.) It is concluded that such breaking strength examinations contribute to a better understanding of the behaviour of substances during compression. These results can be very useful both in preformulation examinations and in tests on the prepared products.

[Influence of viscosity on drug release from ointments, creams, gels and emulsions]. / A viszkozitás hatása kenöcsök, krémek, gélek és emulziók gyógyszerleadására.

The authors studied the drug release from high number of water-free ointments, creams, emulsions and hydrogels. They targeted to find correlation between the viscosity of these pharmaceutical forms and their drug release. Neutral oil was the lipophilic phase of emulsions, the emulsifiers were from Tween and Tagat series. The creams tested consisted of ESMA ointment, Teginacid and/or Softisan emulsifiers and water in 60-80 w/w%. The drug release from Eudispert, methyl-cellulose and hydroxy-ethylcellulose gels was studied. The applied active ingredients were as follows: griseofulvin, sulfadimidine, salicylic acid and ephedrine hydrochloride. Relevant literature suggest a reciprocal correlation between the viscosity of ointments and the quantity of the released drugs. The authors confirmed the general validity of this correlation in case of the following preconditions: if the solubility and distribution of drug do not change along with the change of viscosity there is reciprocal ratio between viscosity and the quantity of drug released. This reciprocal correlation prevails only in a small range of viscosity, that is in systems resembling Newton's liquids. In cases of ointments and gels of higher viscosity a reciprocal relationship exists between the logarithm of viscosity and the quantity of drugs released.

[Use of galactomannan to produce hydrophilic matrix tablets]. / Galaktomannán felhasználása hidrofil mátrix tabletták elöállításában.

Galactomannan currently seems to be a very promising auxiliary. The aim of the present work was to examine the applicability of this auxiliary in tablet-making. Galactomannan is a polysaccharide composed of galactose and mannose, which is distributed by the Swiss firm Meyhall under the name Meyprogat. The products are numbered according to their molecular weight and polymeric degree. Thus, Meyprogat 7, 30, 60, 90, 120 and 150 can be discriminated. It is used in many areas, for example in the food industry as a stabilizing agent, and in medical therapy to cure diabetes and hyperlipidaemia. In pharmaceutical technology, it is used in low concentration (5-10%) as a disintegrant agent and in high concentration (25%) as binding agent. It is able to form a hydrophilic matrix, which results in sustained release. Theophylline was chosen as model agent. After the preformulation examinations, granulations were made by a wet method, and after this tablets were formed. Examinations were made of the granulations, the physical parameters of the tablets were determined, and the release of the effective agent from the tablets was studied. The following conclusions were drawn: 1. Galactomannan yields tablets with very good hardness. 2. Galactomannan is suitable for the formation of hydrophilic matrix tablets. Through use of this macromolecular agent, the rate of dissolution can be influenced in accordance with the desired purpose.

[Formulation of diazepam suppositories, results of rheological and biopharmaceutical studies. 1. Rheological study of the used suppository bases]. / Diazepám-tartalmú végbélkúpok formulálása, reológiai és biofarmáciai vizsgálatának tapasztalatai. 1. Az alkalmazott kúpalapanyagok reológiai tanulmányozása.

The rheological properties of four lipophilic and three hydrophilic suppository bases were studied. The flow and viscosity curves, the initial, equilibrium and plastic viscosity as well as the Bingham's yield value of the systems were determined. It was found that the viscosity curves had two different parts in the examined shearing rate range: the part of greater rise described a definitive destruction of the system, while the part of smaller rise represented an equilibrium state. The values of the rheological parameters of the lipophilic and hydrophilic systems showed a definite difference, which was explained by the greater association of the hydrophilic bases.

[Formulation of diazepam suppositories, results of rheological and biopharmaceutical studies. 2. In vitro membrane diffusion and in vivo absorption results]. / Diazepám-tartalmú végbélkúpok formulálása, reológiai és biofarmáciai vizsgálatának tapasztalatai. 2. In vitro membrándiffúziós és in vivo felszívódási eredmények.

In the first part of the publication the rheological properties of the vehicles used for the production of suppositories were studied in order to determine the ideal parameters for formulation. In this part a detailed methodology and the results of the in vitro membrane diffusion and in vivo bioavailability studies, are presented. The results confirm a general correlation between the in vitro and the in vivo findings. It seems that hydrophilic macrogol-mixture with great molecular mass can be recommended as the optimal vehicle for formulation of diazepam suppositories.

Conditions of cyclodextrin complexation.

In the past 20 years, cyclodextrin (CD) research has achieved considerable results, as indicated by the large number of publications and patents, the six international symposia on CDs, the new dosage forms of medicines prepared with CDs, etc. Sufficient data have accumulated to permit a survey of the most important conditions of CD complexation. Further, an account is presented of the success of precipitation of the complex involving furosemide and beta-CD.

[Research work in the Department of Pharmaceutical Technology of the Albert Szent-Györgyi Medical University]. / Kutatómunka a SZOTE Gyógyszertechnológiai Intézetében.

A short review is given of the research carried out in recent years in the Department of Pharmaceutical Technology headed by the author on the occasion of the 75th birthday of Professor Károly Nikolics. The main results of the scientific activities performed in the four research groups are reported and a few important references to literature are made.

[Formulation and in vitro investigation of antibacterial vaginal suppositories. Part 1. Considerations in selecting the vehicle. Methods and results of the physical examination]. / Antibakteriális hatású vaginális kúpok formulálása és in vitro vizsgálata. 1. Az alapanyag megválasztásának szempontjai. Fizikai vizsgálati módszerek és eredmények.

Vaginal suppositories frequently used in gynaecological therapy were studied. Several antibacterial pharmacons are used for the topical treatment of vaginitis of various origins. However, the choice of the vaginal suppository base was often considered to be of minor importance for a long time. In view of the fact that the liberation of the given active substance and the subsequent therapeutic effect may be improved or inhibited by the vehicle, their aim was to find the optimal suppository base for vaginal suppositories containing sulphadimidine, chloramphenicol and gentamicin-sulphate by means of in vitro experiments. On the basis of breaking hardness, disintegration time and spreading properties the French Suppocire NA product, and compositions of macrogols with lower molecular weight proved to be the best lipophilic and hydrophilic bases respectively.

[Formulation and in vitro investigation of antibacterial vaginal suppositories. Part 2. In vitro membrane diffusion and microbiologic studies]. / Antibakteriális hatású vaginális kúpok formulálása és in vitro vizsgálata. 2. In vitro membrándiffúziós és mikrobiológiai vizsgálatok.

After the physical parameters had been determined, the in vitro drug liberation from vaginal suppositories containing 100 mg of antibacterial agent (sulphadimine, chloramphenicol, gentamicin-sulphate) was studied by membrane diffusion and microbiological methods. Among the vehicles available in Hungary the hydrophylic Massa macrogoli was found to be the best for this purpose. Among the lipophilic bases the in vitro drug liberation of the French Suppocire NA product was significantly better (p < 0.05) compared to the other lipophilic bases. This vehicle is recommended by the authors for the topical treatment of vaginitis, as these suppositories have the further advantage that they can easily be produced on a magistral, galenical or industrial scale as well. In the first part of the publication the formulation and some important physical parameters of lipophilic and hydrophilic antibacterial suppositories for vaginal use were described. In the present paper the drug liberation ability of the compositions with proper physical parameters was studied. The published results were obtained from measurements performed 1 week after formulation.

[Formulation and analysis of suppositories containing papaverine hydrochloride. Part 1. Choice of the optimal vehicle and determination of the physical parameters of the suppositories]. / Papaverinium-klorid-tartalmú végbélkúpok formulálása és vizsgálata. I. Az optimális vehikulum kiválasztása és a kúpok fizikai paramétereinek meghatározása.

Suppositories containing 0.10 g papaverine hydrochloride were made with moulding technology to produce spasmolytic effect. The optimal vehicle was tried to be found for these suppositories. During the experiments 12 different suppository masses were used, including lipophil and lipohydrophil vehicles as well as vehicles with low and high hydroxyl numbers. Five different kinds of physical parameters were determined: melting and drop points, disintegration and special penetration times and breaking hardness. The physical parameters of suppositories without active substance and containing papaverine were examined separately. After 6 months of storage the greater part of the masses showed unfavourable changes (after-hardening, increase of the disintegration time, etc.). In the end the Estaram 299 mass, a triglyceride type of mass with a low hydroxyl number was found satisfactory in every respect, either in itself or combined with 5% Estasan neutral oil.

[Formulation and analysis of suppositories containing papaverine hydrochloride. Part 2. In vitro membrane diffusion studies]. / Papaverinium-klorid-tartalmú végbélkúpok formulálása és vizsgálata. II. In vitro membrándiffúziós vizsgálatok.

Rectal suppositories with 0.10 g/2.0 g Papaverine hydrochloride content were made with 12 different vehicles. The membrane diffusion method was used to study the factors influencing the in vitro drug liberation. The Polysorbate 20 and 61 tenside pair, the optimal concentration of which was 5% each, was found to influence diffusion favourably. Neutral oils softening the consistency (Miglyol 812 and Estasan), similarly in 5%, also had a favourable effect on the in vitro diffusion by increasing the spreading properties. As to the lipophil suppository masses with high and low hydroxyl numbers, only the latter could be used favourably. The 6-month-long storage resulted in drug retention in several experimental series. Correlation was found in several cases between the physical parameters of the suppositories and their in vitro drug liberation. Finally, with the help of linear regression calculation and in view of the in vitro relative bioavailability values the optimal vehicle is suggested for the formulation of suppositories containing Papaverine hydrochloride. The triglyceride type Estaram 299 was found to be the most suitable in every respect, either in itself or combined with 5% neutral oil.

[Deformation phenomena occurring during compression. III. Changes of maximal compression strength in quasi-static condition]. / Adatok a préselés során bekövetkezö deformációs jelenségek tanulmányozásához. III. A Kvázi-sztatikus állapotban mért maximális préselési eröváltozás vizsgálata.

Four materials of different properties in respect of compressibility, lactose, sodium chloride, microcrystalline cellulose (Avicel PH 101) and so-called simple granulate were investigated. In function of time and that of actual pressing force decrease of axial force on upper punch were measured in quasi-state. Evaluating relations it was established that both pressing time and pressing force had influence on deformation structural changes occurring inside compressed form. Furthermore, summing up of results showed that useful conclusions could be drawn from diagrams--which represented decrease of force--to compressibility properties of materials too.

[Biopharmaceutical study of aminophenazone-containing suppositories. 1. Experimental materials and methods, determination of physical qualities of the suppositories]. / Aminofenazon-tartalmú kúpok biofarmáciai vizsgálata. I. Kísérleti anyagok és módszerek ismertetése, a kúpok fizikai jellemzöinek meghatározása.

Suppositories containing aminophenazone in quantities of 0.30 g/2 g were prepared by pouring technology. Two kinds of lipophilic suppository masses Witepsol W 35 and Estarinum 299 have been used as vehicles. Both of suppository bases are official in Ph. Hg. VII. As ingredients ten sorts of liquid tensides in concentrations of 5% have been applied. Experimental methods have been described: compression stability, disintegration time, special penetration time and drug release of suppositories by membrane diffusion method. Results of determinations have been discussed in the second part of the publication. On the basis of experimental results it has been established that the physical parameters of Massa Estarinum 299 had proved to be more advantageous. In 5% concentrations tensides softened consistency of suppositories favorably and shortened disintegration time beneficially in the case of both vehicles. The authors think that special penetration time is more suitable for measuring "disintegration" of suppositories of high powder content at 37 degrees C than the classical disintegration time.

[Biopharmaceutical study of aminophenazone-containing suppositories. 2. Results of in vitro drug release and in vivo drug absorption]. / Aminofenazon-tartalmú kúpok biofarmáciai vizsgálata. II. Az in vitro gyógyszerleadás és az in vivo gyógyszerfelszívódás eredményei.

Ten kinds of surface active ingredients of Th. Goldschmidt AG. (Essen-FRG) in concentrations of 5% were mixed with Witepsol W 35 and Massa Estarinum 299 suppository masses of Hüls-Troisdorf AG. Werk (Witten-FRG) which are official in Hungary. According to the authors the above tensides, which have been used advantageously first of all in ointments, creams and cosmetic preparations, can also be applied in rectal preparations. In the publication of two parts it has been established that these ingredients influence physical parameters of suppositories beneficially. They always increase significantly in vitro diffusion values and in some cases with order of magnitude. Massa Estarinum 299 containing 5% of Emulgator BTO proved to be the best in case of chosen suppositories containing aminophenazone. Correlation between in vitro and in vivo investigations has shown the importance of correct selection of base and ingredient materials in biopharmaceutical work.

[Deformation phenomena occurring during compression. II]. / Adatok a préselés során bekövetkezö deformációs jelenségek tanulmányozásához. II. Elektronmikroszkópos vizsgálatok.

Compressed forms were prepared from sodium chloride of given granule size with mildly concave punches applying 4, 12 and 20 kN pressing force. Pressing was regulated in order to get maximum pressing force effect for 0.1 s, 30 s and 60 s. Textures of side of compressed forms as well as edge and middle of surface of compressed forms were investigated by scanning electron microscope. Photos made with different enlargement have proved that secondary structural changes have begun (colour changes, new crystals have come to being etc.) on side stronger but also well observable on surface of compressed forms which in function of pressing force and that of time of pressing force effect have increased and grown considerably.