Effects of temperament during handling and social rank on the blood biochemical parameters of common eland (Taurotragus oryx).

Large herbivores are subject to handling and social stress in captivity. These may affect blood biochemical values, which motivated this research. Twelve healthy common eland (Taurotragus oryx) were monitored for 12 months. The animals were handled monthly, and blood samples were collected. Samples from every second month were analysed for 14 blood biochemical parameters. Temperament throughout the handling, as the summation of various behavioural responses, was calculated as a proxy of the stress generated during handling. Social behaviour was recorded each month, and the agonistic interactions were used to calculate the social rank, which was considered a proxy of social stress. Generalised Linear Mixed Models were designed to test the effects of temperament and social rank on the blood biochemical parameters while keeping sex, age, body condition, and body weight as covariates. The results show that the temperament during handling influences blood levels of albumin, alkaline phosphate, blood urea nitrogen, glucose, total bilirubin, and total protein; however, social rank has little influence, affecting just albumin. The ranges observed in the values of these biochemical parameters were still within their reference intervals, implying the absence of pathology or physiological problems during the study. The results suggest that blood biochemical values of physically restrained common eland should be carefully interpreted, even in animals already habituated to routine handling. On the contrary, social rank has low effects on the blood biochemical parameters.

Extending the interval between second vaccination and slaughter: I. Effects on growth, scrotal size and stress responses of immunocastrated ram lambs.

Immunocastration provides a less invasive means of castrating lambs. Considering increasing consumer awareness, the efficacy of this technique on commercial slaughter lambs needs to be further investigated and its effects on growth and stress responses need to be established. This study compared the growth rate, testes size and stress responses of immunocastrated lambs with that of lambs physically castrated with a Burdizzo clamp, as well as intact rams. A total of 40 Dohne Merino ram lambs (average live weight = 45.4±3.68 kg) were randomly allocated to the following four treatment groups: control (intact; R), Burdizzo-castrated (on day 2; B), immunocastrated with a 4-week (ICS4), or a 6-week (ICS6) interval between the second immunocastration vaccination and slaughter. Within the immunocastration treatments, the reaction to vaccination was assessed through injection site scoring, recording the local injection site surface temperature and assigning a walking score. The response to Burdizzo castration was assessed by scoring the reaction during the procedure, testes palpation reaction, walking gait and measuring testis temperature. Additional parameters recorded included BW, serum cortisol concentration, scrotal circumference and rectal temperature. Pain behaviours were described for the short-, medium- and long-term effects after the two methods of castration. Predominantly, tissue-hardening and bruising occurred at the injection sites of immunocastrates, but little effect was observed on walking comfort and no effect on injection site temperature or rectal temperatures. After Burdizzo castration, lambs spent more time in abnormal postures, and from day 3 (D3) to D8 of the trial, discomfort was observed during testes palpation and walking in B lambs. Serum cortisol concentrations were elevated in B lambs on D3 and D15, indicating physiological stress. Thus, immunocastration improved the welfare of castrated lambs as assessed by cortisol secretion, scrotal swelling and pain behaviours, without influencing growth rate.

Extending the interval between second vaccination and slaughter: II. Changes in the reproductive capacity of immunocastrated ram lambs.

Immunocastration improves the welfare of castrated commercial slaughter lambs; however, the time-point at which this technique influences semen quality and sperm production has not yet been established for various vaccination schedules. Furthermore, the effect of extended intervals between second vaccination and slaughter needs to be investigated regarding continued testosterone suppression in immunocastrated lambs. The effect of extending the interval between second immunocastration vaccination and slaughter from four to six weeks on the reproductive capacity of Dohne Merino lambs was examined. A total of 40 Dohne Merino lambs were stratified according to initial weight (45.4±3.68 kg) and randomly assigned to four treatments that included intact control rams (R), Burdizzo-castrated lambs (B) and lambs immunocastrated with either four (ICS4) or six (ICS6) weeks between second vaccination and slaughter. Blood and semen samples were collected throughout the study period to determine serum testosterone concentrations, evaluate semen quality and assess sperm viability. Semen samples from R showed improvement over the trial. Throughout the collection period, B lambs had low serum testosterone concentrations, poor sperm motility and sperm viability, as expected. However, a slight increase in the percentage of live sperm in semen samples from B lambs towards the end of the collection period indicated poor success rates of the technique in some lambs. Burdizzo-castration also caused testes tissue necrosis and abscessing, indicating physiological stress. Semen appearance scores varied for both immunocastrated treatments, but the mass motility scores decreased over time. The ICS6 lambs showed a consistent and continuous decline in serum testosterone concentrations and sperm viability, with an increased percentage of dead abnormal sperm in the semen samples at the end of the study. The ICS4 treatment was successful in interrupting serum testosterone production and reducing semen quality; however, not as consistently as the ICS6 treatment. Primary immunocastration vaccination influenced serum testosterone concentrations but consistently low levels were only realised for both treatments after secondary vaccination. Although all castration treatments influenced testes size and colour, the six-week vaccination-to-slaughter interval caused a greater decrease in testes cut surface L* (lightness) colour values and in seminiferous tubule circumference. Extending the interval between second immunocastration vaccination and slaughter resulted in a more consistent and reliable influence on reproductive capacity of immunocastrated lambs. Thus, immunocastration is a suitable alternative to Burdizzo-castration regarding the interruption of testosterone production and testis functioning.

Growth responses of entire and immunocastrated male pigs to dietary protein with and without ractopamine hydrochloride.

The interaction between dietary balanced protein, ractopamine (RAC) and Improvac (IMP) on the growth response of 120 individually penned male PIC© pigs was evaluated. The pigs entered the trial at 16 weeks of age and were assigned to 12 treatments using a 2×2×3 factorial design. Three balanced protein diets, formulated with standard illeal digestible lysine levels of 7.50 (low), 9.79 (medium) and 12.07 g/kg (high), were fed from 20 weeks. Improvac was administered at 16 and 20 weeks, the booster being given 4 weeks before slaughter. Ractopamine was supplemented at 10 mg/kg to the applicable treatments from 20 weeks. Live weight, backfat depth and food intake were measured on a weekly basis. Primary vaccination had no influence on the parameters measured. Immunocastration, RAC and higher protein diet treatments increased weight gain, but food intake was increased only with the use of IMP. Although weight gain increased in IMP-treated males, the increased feed intake resulted in their feed conversion efficiencies (FCE) being inferior to the intact controls. Feeding RAC only benefitted FCE when a high or medium protein diet was fed. Immunocastrates deposited more backfat after the booster vaccination than did entire males. Thus the cost of using RAC, IMP and of increasing dietary protein content needs to be weighed up against the additional revenue generated through the use of these interventions.

Colpopexia al ligamento sacroespinoso con CapioTM; cirugía, resultados y evolución de pacientes / Sacroespinous ligament colpopexy with CapioTM; surgery patient outcomes and evolution

Introducción: El prolapso genital femenino altera significativamente la calidad de vida de la mujer. El prolapso apical es el segundo más frecuente después del defecto de pared anterior y la colposuspensión al ligamento sacroespinoso es una de las técnicas quirúrgicas descritas para su tratamiento. Objetivos: Determinar la factibilidad de la corrección del prolapso apical en pacientes sometidas a la colposuspensión al ligamento sacroespinoso, utilizando el dispositivo de captura de sutura CapioTM. Materiales y métodos: Análisis retrospectivo de pacientes intervenidas desde junio de 2015 a junio de 2016, en la unidad de piso pélvico del Hospital Luis Tisné Brousse, basándose principalmente en la evaluación del punto C del Prolpase Organ Pelvic Quatinfication (POP-Q). Resultados: Se intervinieron 15 pacientes, con edad promedio de 60,7 ± 6,8 años. Todas presentaron prolapso genital estadio III o IV. El seguimiento se realizó entre 3 y 13 meses después de la cirugía. Ninguna presentó complicaciones graves durante ni después de la cirugía y sólo una paciente recidivó. Conclusiones: La colposuspensión al ligamento sacroespinoso con CapioTM, es una técnica factible, segura y eficaz para el tratamiento del prolapso apical, sin embargo, es necesario mayor tiempo de seguimiento y estudios comparativos con otras técnicas de colposuspensión.

Introduction: Female genital prolapse significantly alter the quality of life of women. The apical prolapse is the second common defect after anterior wall and the colposuspension to sacrospinous ligament is one of the described surgical techniques for its treatment. Objective: To determine the feasibility of apical prolapse correction in patients undergoing sacrospinous colposuspension using the suture capture device CapioTM. Methods: Retrospective analysis of patients undergoing this surgery from June 2015 to June 2016, including an objective assessment focused mainly in the C point of Prolapse Organ Pelvic Quatinfication (POP-Q) and a subjective evaluation of the patient. Results: 15 patients, of which only 11 were able to complete follow-up, were included. The mean age of the patients at the time of surgery was 60.7 ± 6.8 years, and all were classified as prolapse stages III or IV. The evaluation was performed in average 6.75 ± 3.39 months after surgery, with a minimum of 3 and a maximum of 13 months. No patient had several complications during or after surgery and only one recurred. Conclusions: The colposuspension to sacrospinous ligament with CapioTM is a safe and effective alternative for the treatment of apical genital prolapse. However, a longer follow-up study is needed, in addition to comparative studies with other colposuspension techniques.

Carcass traits and cutting yields of entire and immunocastrated pigs fed increasing protein levels with and without ractopamine hydrochloride supplementation.

The objective of this study was to determine the effects of increasing balanced protein, with and without ractopamine hydrochloride (RAC), in the finisher diets of immunocastrates on their carcass cutting yields and respective muscle, fat, and bone proportions. Carcass traits and yields of 120 individually housed entire male pigs and immunocastrates were evaluated following a 2 × 2 × 3 factorial design. Vaccination occurred at 16 and 20 wk of age and slaughtering at 24 wk. Up until 20 wk of age, all pigs received a commercial grower diet. Low-, medium-, and high-protein (7.50, 9.79, and 12.07 g standardized ileal digestible [SID] lysine/kg, respectively) diets were then fed for the last 28 d with RAC supplemented at 0 or 10 mg/kg. Immunocastration and RAC supplementation increased ( = 0.003 and = 0.017, respectively) the live weight at slaughter. The interaction between sex and protein ( = 0.039) for caliper backfat depths showed greater backfat depths in immunocastrates fed medium protein whereas RAC decreased ( = 0.027) the caliper backfat depth. Feeding RAC increased the trotters ( = 0.040), tenderloins (fillets; < 0.001), shoulder ( = 0.002), hindquarter ( = 0.026), loin ( = 0.028), and belly ( = 0.044) percentages. The shoulder ( < 0.001), hindquarter ( < 0.001), and loin ( = 0.005) muscle percentages were increased and the hindquarter fat percentages were decreased ( = 0.032) with RAC supplementation. Immunocastration increased the belly cut ( = 0.006), loin fat ( < 0.001), and belly fat ( < 0.001) percentages. Therefore, carcass cutting and lean yields can be improved by RAC supplementation while decreasing the backfat depth, and the increase in backfat due to immunocastration could be avoided with the correct dietary protein level.

Physical meat quality and chemical composition of the Longissimus thoracis of entire and immunocastrated pigs fed varying dietary protein levels with and without ractopamine hydrochloride.

Physical and chemical attributes of the Longissimus thoracis (LT) of 96 PIC(©) entire (E) and immunocastrated (C) pigs were evaluated. The study followed a 2 × 2 × 3 factorial design where three diets of low, medium and high proteins (7.50, 9.79 and 12.07 g digestible lysine/kg) were fed either with (10mg/kg) or without ractopamine (RAC) for the last 28 days of growth. Vaccination of C occurred at 16 and 20 weeks and slaughtering at 24 weeks of age. The LTs were analysed for moisture, protein, fat and ash contents as well as CIE L*, a*, b* colour, drip loss, cooking loss and Warner-Bratzler shear force (WBSF). Various sex and protein interactions were observed for LT protein content, L* values and WBSF. Cooking loss was decreased in C and by the medium protein diet. Feeding RAC increased WBSF values, whilst decreasing a* and b* values. However, the differences observed are minor and might be considered negligible when evaluated by a consumer.

Development and evaluation of nasal formulations of ketorolac.

Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 microm to 63 microm did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.

Ophthalmic drug delivery systems--recent advances.

Eye-drops are the conventional dosage forms that account for 90% of currently accessible ophthalmic formulations. Despite the excellent acceptance by patients, one of the major problems encountered is rapid precorneal drug loss. To improve ocular drug bioavailability, there is a significant effort directed towards new drug delivery systems for ophthalmic administration. This chapter will focus on three representative areas of ophthalmic drug delivery systems: polymeric gels, colloidal systems, cyclodextrins and collagen shields. Hydrogels generally offer a moderate improvement of ocular drug bioavailability with the disadvantage of blurring of vision. In situ activated gel-forming systems are preferred as they can be delivered in drop form with sustained release properties. Colloidal systems including liposomes and nanoparticles have the convenience of a drop, which is able to maintain drug activity at its site of action and is suitable for poorly water-soluble drugs. Among the new therapeutic approaches in ophthalmology, cyclodextrins represent an alternative approach to increase the solubility of the drug in solution and to increase corneal permeability. Finally, collagen shields have been developed as a new continuous-delivery system for drugs that provide high and sustained levels of drugs to the cornea, despite a problem of tolerance. It seems that new tendency of research in ophthalmic drug delivery systems is directed towards a combination of several drug delivery technologies. There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but which at the same time slow down the elimination of the drug. Combination of drug delivery systems could open a new directive for improving results and the therapeutic response of non-efficacious systems.

Emulsion formulations of testosterone for nasal administration.

The nasal route has received a great deal of attention due to the many advantages of nasal delivery over parenteral administration. The male sex hormone testosterone is ineffective when administered orally due to its gut wall and first-pass metabolism. Therefore, an alternative method for delivery would be the intranasal route, if the lack of aqueous solubility can be overcome. In this study a new approach to emulsion formulations of the drug has been proposed based on the hypothesis that increased absorption is possible upon solubilization of the drug and/or prolongation of the formulation residence time in the nose. Three differently charged testosterone submicron size emulsion formulations with various zeta potentials (+24.8, -23.0 and 0.06 mV) were prepared as nasal spray formulations. A dose of approximately 3.8 mg testosterone per rabbit was administered to four rabbits and the bioavailability of the emulsion formulations was assessed and compared with an i.v. formulation via solid-phase extraction, followed by an HPLC analysis method. Statistical analysis of the normalized data indicated a bioavailability of 55, 51 and 37% for positively, negatively and neutrally charged emulsions respectively. The results of this study strongly suggest that emulsion formulations have some potential to be considered for nasal delivery. Further, both the positively and negatively charged emulsion formulations provided a better bioavailability than the neutral charged emulsion, probably indicating that the charged particle interactions between emulsion globules and the mucus layer prolong the contact of drug with nasal membrane thus enhancing drug absorption.

Codiffusion of propylene glycol and dimethyl isosorbide in hairless mouse skin.

The in vitro percutaneous fluxes of propylene glycol (PG), cis-oleic acid (OA) and dimethyl isosorbide (DI) were determined and their effect on nifedipine (N) flux and lag time evaluated. PG, OA and DI flux through hairless mouse (HM) skin was measured in vitro by beta-scintigraphy and N permeation was measured by HPLC under finite and infinite dose conditions. Evaluation of each of the solvents separately showed that pure DI possessed the inherent ability to traverse the skin (12% in 24 h). For the tested formulation after 24 h, 57% of the PG and 40% of the DI had permeated across the skin with nearly linear permeation between 4 and 18 h and the relative order of permeation was PG > DI > N. DI permeation was further aided in the presence of PG and OA. N flux was dependent on concomitant solvent permeation. Over a 24-h test period a dose dependent response was observed for N, with 4.9-15.6 mg of N delivered from the lowest and highest doses, respectively, and the highest dose yielding zero-order flux of 146 (g/h per cm2).

The influence of the enhancer dimyristoylphosphatidylglycerol and formulation factors on the nasal absorption of salmon calcitonin.

The objective of this investigation was to study the effect of the phospholipid dimyristoylphosphatidylglycerol (DMPG) on the intranasal absorption of the polypeptide salmon calcitonin (sCT). DMPG was included as an absorption enhancer for salmon calcitonin in a 0.03 M acetate buffer at pH 4 in a nasal spray formulation. The absorption of sCT was studied as a function of NaCl concentration from 0.045 to 0.3 M. Serum calcitonin was determined using a double-antibody radioimmunoassay (RIA). The presence of the phospholipid demonstrated a significant difference in the intranasal bioavailability of salmon calcitonin. The results showed that DMPG enhanced the nasal absorption of sCT by approximately twofold at a salt concentration of 0.045 M. However, higher salt concentrations in the formulation demonstrated a decrease in the absorption-enhancing effect of DMPG. The effect of DMPG on the calcium-lowering effect of sCT was also studied. There was no significant difference in the hypocalcemic activity of sCT in the presence of DMPG. In addition, it was found that increasing the viscosity of those formulations containing DMPG did not further increase the nasal bioavailability of sCT.

Ketorolac tromethamine and ketoprofen suppositories: release profiles and bioavailability of a cocoa butter base formula in rabbits.

Ketorolac tromethamine suppositories (30 mg) and ketoprofen suppositories (50 mg) were made by the fusion method with various bases such as cocoa butter, Witepsol H15, Witepsol W25, Witepsol W35, Witepsol E75, Suppocire AML and Hydrokote AP5-1. Also, ketorolac tromethamine and ketoprofen suppositories were prepared using Eudragit L100 and propylene glycol. The release rates for both ketorolac tromethamine and ketoprofen suppositories in Sorensen's phosphate buffer pH 7.4 were determined and found to be: cocoa butter greater than Witepsol H15 greater than Witepsol W25 greater than Suppocire AML greater than witepsol W35 greater than Hydrokote AP5-1> Witepsol E75. Drug-release studies showed that ketorolac tromethamine demonstrates faster release profiles from these selected bases in comparison to those seen for ketoprofen. Analysis of the relaease kinetics for ketorolac tromethamine and ketoprofen from the various bases suggests that a combination of release mechanisms such as melting of the base followed by partititoning of the drug, along with some diffusion of the drug from the base to the dissolution media, seems to be operative in these systems. The absolute bioavailabilty of the suppository formulaion made with ketorolac tromethamine in cocoa butter base was found to be 61% in rabbits.

Effect of cyclosporine A formulations on bovine corneal absorption: ex-vivo study.

The purpose of this study was to evaluate, in an ex-vivo study, the absorption of cyclosporine A on bovine cornea after 24 h contact with various drug delivery systems containing 1% cyclosporine A and in comparison with an olive oil formulation as the reference vehicle for cyclosporine A. The different formulations studied were poly(acrylic acid) polymeric gels in aqueous/non-aqueous solvents, polyisobutylcyanoacrylate nanocapsules, and a combination of both formulations. The histological effects of these formulation on corneal cells after 24 h of contact were also studied. The lowest absorption rate of cyclosporine A was found using olive oil with a percent absorption of 2.52 +/- 1.52% (259 +/- 171 micrograms/g cornea). The three formulations developed for this study, nanocapsules, poly(acrylic acid) polymeric gel and nanocapsules gel showed significantly better absorption of CsA than olive oil, with a mean percent absorption of 5.81 +/- 2.04% (621 +/- 218 micrograms/g cornea), 6.09 +/- 2.93% (651 +/- 313 micrograms cornea) and 7.92 +/- 2.55% (847 +/- 273 micrograms/g cornea) respectively. As we studied the penetration of cyclosporine A into the different layers of the cornea, we observed that for all formulations, CsA remained at the corneal surface and did not penetrate the whole cornea. The histological study showed that olive oil, nanocapsules and poly(acrylic acid) gel in aqueous/non-aqueous solvents show some modifications on the cornea, contrary to the nonocapsules gel which did not indicate any toxic effect. The nanocapsule gel, with the highest percent absorption along with its margin of safety on the cornea, seems to present a new promising drug delivery system for ocular administration.

Release kinetics of liposome-encapsulated ganciclovir after intravitreal injection in rabbits.

This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped ganciclovir could prolong intraocular therapeutic levels when it is compared to the intravitreal injection of a simple solution of the drug. New Zealand white rabbits were given an intravitreal injection of the drug solution and of liposome-encapsulated ganciclovir. The intravitreal clearance of ganciclovir was determined after a single injection of either the drug solution (200 micrograms/0.1 mL) or the liposomally-entrapped (with 41% load; 82 micrograms drug load and 118 micrograms free) ganciclovir. The ganciclovir vitreal concentrations were measured at various time intervals for a period up to 43 days using an HPLC method. The results of this study clearly demonstrated that prolonged intravitreal drug levels (above the mean inhibitory dose of cytomegalovirus of 1 microgram/mL) after administration of the liposome-entrapped ganciclovir and estimated to continue beyond 30-43 days. The injection of the 200 micrograms/0.1 mL of drug solution showed a mean vitreous concentration which was higher than the ID50 only for 55 h. The disappearance rate constant for the liposome-encapsulated injections was approximately 22 x slower than simple drug solution injections (controls). No evidence of retinal toxicity was found by clinical or light microscopy examination of the treated eyes.

Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. III: The effect of the coat thickness on the adsorptioncapacity of the coated charcoal and its adsorptivity to small and middle size molecules.

In this study, the effect of the coat thickness of polyacrylate-polymethacrylate copolymer on the adsorption capacity of activated charcoal to methylene blue as a model marker was investigated by constructing both Langmuir and Freundlich isotherms. It was found that the coat thickness significantly affected the adsorption coefficient of the coated charcoal to methylene blue as is reflected by the attractive forces between the adsorbent and the adsorbate. This effect is understandable as the membrane will act as a barrier between the adsorbent and the adsorbate. The coat thickness also had some effect on the adsorption capacity of activated charcoal but not as much as it affected the adsorption coefficient. The data followed the Freundlich isotherm more closely than the Langmuir equation. The effect of the coat thickness on the adsorption of selected drugs of different molecular size was also investigated using theophylline, paracetamol, sodium phenobarbital, creatinine and vitamin B12 as model drugs. The results showed that the adsorption patterns of theophylline, paracetamol and sodium phenobarbital were more or less similar. The apparent coating thickness did not affect the extent of adsorption of these model drugs and there was little effect on the adsorption rate especially during the first 15 min. The adsorption of vitamin B12 and creatinine showed completely different patterns which are discussed in detail.

Development of a new non-surgical perfusion technique for evaluation of nasal drug delivery.

A new non-surgical perfusion technique was developed to evaluate nasal absorption using the rabbit as an animal model and insulin as a model drug. For these studies 20 ml of insulin solution (10 U/kg + 0.05% Na taurocholate) was perfused for 3.5 hours at a rate of 10 ml/hr. Spray formulations containing different levels of insulin (1.25, 2.5, 5 and 10 U/kg) and sodium taurocholate (0.05 and 1.0%) were evaluated in the same animal model. Insulin loaded polyacrylic acid microparticles were administered in 1% gel formulation to determine the comparative effect of insulin. The absorption of insulin was measured by glucose reduction. Pharmacodynamic parameters were determined relative to subcutaneously injected insulin (0.25 U/kg). The new non-surgical perfusion technique proved to be easier to control and more reproducible than the formerly used perfusion model while providing comparable results. The maximum relative absorption was observed for the 1.25 U/kg spray containing 1% NaTC. The polyacrylic acid gel formulation containing insulin loaded microparticles (10 U/kg) resulted in lower hypoglycemic effect compared to the spray formulations and subcutaneous injection.

Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. II. Drug removal and polymer compatibility studies.

The newly developed system of polyacrylate-polymethacrylate-coated charcoal, filled in a column has been tested for its efficiency in removing theophylline, as a model drug both from a buffer solution pH 7.4 and human plasma using a closed-circuit apparatus. Preliminary testing determined the capacity of the charcoal column and the effect of circulation rate of the buffer solution on the clearance of theophylline. It was found that the circulation rate does not significantly affect the clearance rate of theophylline, while the concentration of drug in the buffer solution has a considerable effect on the clearance of the drug, presumably due to the saturation of the column. The clearance of the drug from plasma in comparison to buffer solution was also investigated. It was found that more than 70 per cent of the drug was removed from the buffer solution within the first 15 min as compared with 65 per cent from plasma; with 95 per cent removed from buffer after 1 h in comparison to 93 per cent from plasma. The blood compatibility of the polymer was studied by incubating various concentrations (5-25 per cent w/v) of the polymer in blood for 30 min at 25 degrees C. A concentration of 5 per cent polymer was also incubated for a series of incubation times. The results indicated that with polymer concentrations up to 15 per cent there is no significant lysis of RBCs in comparison to a blank.(ABSTRACT TRUNCATED AT 250 WORDS)

Transdermal drug delivery systems of albuterol: in vitro and in vivo studies.

In vitro and in vivo experiments were conducted with double- and single-layer albuterol transdermal pads designed for once-a-day application. In the in vitro experiments, dissolution of albuterol from pads and permeation of albuterol through hairless mouse skin were monitored. In the in vivo experiments, pads were applied to the chest area of four female rhesus monkeys (Macaca mulata), and an albuterol aqueous solution was injected into the saphenous vein of the same animals in a crossover design. The amount lost from pads applied to monkeys was monitored by analysis of pad residue. Blood samples were withdrawn at regular intervals and analyzed by a high-performance liquid chromatography-fluorescence method. Skin irritation due to the pad was measured by a modified Draize score test. The amounts released from the two formulations were similar. The amount released was, however, dependent on the technique used and decreased in the following manner: pad dissolution greater than in vivo amount lost from pads applied to monkeys greater than in vitro permeation through hairless mouse skin. The pharmacokinetic parameters determined after intravenous and transdermal administration were as follows: terminal half-life, 2.26 +/- 0.45 h; apparent volume of distribution, 1935 +/- 37.2 mL.kg-1; and total body clearance, 612.0 +/- 118 mL.h-1.kg-1. The average concentrations in serum after application of single- and double-layer pads were 44.60 +/- 16.40 and 62.50 +/- 8.00 ng/mL, respectively. Further, the amount lost from pads applied to monkeys correlated with the respective amount absorbed in monkeys, as calculated from the average concentration in serum and clearance.(ABSTRACT TRUNCATED AT 250 WORDS)