Release Of Salbutamol Sulphate Research Articles

Dissolution of fine particle fraction from truncated Anderson cascade impactor with an enhancer cell

Dissolution testing for inhalers were previously conducted either on unfractionated drug-carrier powders or drug of specific aerodynamic particle size. In this study, the collection of the full fine particle fraction (FPF) was attempted on a single stage. Capsules containing 30 mg of 2% salbutamol sulfate (SS) was tested to have a FPF of 9 ± 1% using the full set of Andersen cascade impactor (ACI) and a modified Rotahaler® capable of achieving 4.0 kPa pressure drop at 60 L/min air flow rate. A truncated ACI comprising the USP throat, pre-separator, stage 0, stage 4, stage F, polytetrafluoroethylene funnel (TF) and small collection plate (sCP) was found to be capable of achieving a FPF of 9% collected on TF and sCP. An adhesive tape was used to collect the FPF from the TF and sCP and held in place by an enhancer cell in a 200 mL round bottom vessel containing 50 mL Gamble’s solution with 0.2 v/v, % Tween 80. Dissolution testing of SS and Seretide® showed burst release of SS and salmeterol while sustained release of fluticasone. This study demonstrated a reproducible method which may be used for evaluation of the full FPF of orally inhaled products.

Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA into inhalable microparticles, which were subsequently characterized as spherical shape with wrinkled surface. The fine particle fraction of the microparticles tested by using the Next Generation Impactor was over 30% without the aid of any carrier, and the in vitro release of SAS lasted for 20h. Compared to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum concentration in plasma was reduced significantly from 2267.7ng/mL to 566.38ng/mL. These results suggested that inhaled HA microparticles could be a promising formulation strategy to enhance the therapeutic efficacy of inhaled medicines.

In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets

The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.

Comparison of spray congealing and melt emulsification methods for the incorporation of the water-soluble salbutamol sulphate in lipid microparticles

Context: Salbutamol sulphate is widely used as bronchodilator for the treatment of asthma. Its use is limited by the relatively short duration of action and hence sustained delivery of salbutamol sulphate offers potential benefits to patients.Objective: This study explores the preparation of lipid microparticles (LMs) as biocompatible carrier for the prolonged release of salbutamol sulphate.Materials and methods: The LMs were produced using different lipidic materials and surfactants, by classical melt emulsification-based methods (oil-in-water and water-in-oil-in-water emulsions) and the spray congealing technique.Results: For the LMs obtained by melt emulsification a lack of release modulation was observed. On the other hand, the sustained release of salbutamol sulphate was achieved with glyceryl behenate microparticles prepared by spray congealing. These LMs were characterized by scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry. The drug loading was 4.72% (w/w). The particle size distribution measured by laser diffraction and electrical zone sensing was represented by a volume median diameter (Dv50) of 51.7–71.4 µm. Increasing the atomization air pressure from 4 to 8 bar produced a decrease of the Dv50 to 12.7–17.5 µm.Conclusions: Incorporation of the hydrophilic salbutamol sulphate into LMs with sustained release characteristics was achieved by spray congealing.

Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery

PurposeThe main objective of this study was to develop a novel aerosolized liposome formulation for pulmonary delivery of anti-asthmatic medication and to explore the relationship between the bioavailability and anti-asthmatic efficacy of such a formulation. Asthma treatment usually requires frequent administration of medication for sustained bronchodilating response. Liposomes are known for their capability for sustained drug release and thus would be a suitable delivery system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol sulfate (SBS) was chosen as the model drug in this study because of its high water solubility and fast absorption after administration.MethodsSBS was efficiently encapsulated into liposomes by the vesicular phospholipid gel technique. SBS permeability across the pulmonary membrane of an Asian toad was determined by in vitro study. Intratracheal administration of liposomes labeled with the fluorescent dye 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a rat model was assessed by a small animal imaging system and pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs using the Konzett–Rössler method.ResultsSBS was efficiently encapsulated into liposomes with encapsulation efficiency as high as 70%. The particle size of the SBS liposome suspension was approximately 57 ± 21 nm. In the in vitro study of permeability across the pulmonary membrane of Asian toads, SBS from liposomes demonstrated a slower transport rate compared to free SBS solution. Pulmonary delivery of liposomes in a rat model showed that the liposomes were effectively distributed in the respiratory tract and lungs, and that the release of SBS from liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted for up to 18 hours, whereas that of free SBS solution was less than 8 hours.ConclusionThe overall results demonstrated that liposomes could increase the concentration and retention time of SBS in the lungs and therefore prolong its therapeutic effect.

The use of response surface methodology for the formulation and optimization of salbutamol sulfate hydrophilic matrix sustained release tablets

The objective of this study was to develop a hydrophilic matrix formulation with in vitro release characteristics similar to Asthalin® tablets and that would sustain the release of salbutamol sulfate over a 12-h period. A central composite design was used as the framework for manufacturing formulations that may be used to understand the relationships between polymer levels and in vitro release characteristics. Tablets were manufactured using wet granulation with Surelease® as the granulating fluid and different levels of Methocel® K100M, xanthan gum, and Carbopol® 974P as matrix-forming materials. In vitro dissolution testing was conducted using USP Apparatus 3 and samples were analyzed using a validated reversed-phase HPLC method. The results revealed that the levels and types of polymers had a significant impact on the rate of drug release from these formulations and that it was possible to optimize the levels of matrix-forming polymers to achieve the desired release characteristics. Statistical design and response surface methodology have been successfully used to understand and optimize formulation factors and interactions that impact the in vitro release characteristics of salbutamol sulfate from a potential multisource sustained release dosage form.

Preparation and Characterization of Salbutamol Sulphate Loaded Ethyl Cellulose Microspheres using Water-in-Oil-Oil Emulsion Technique.

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of a highly water/soluble drug, salbutamol sulphate by (water in oil) in oil emulsion technique using ethyl cellulose as the retardant material. Various processing and formulation parameters such as drug/polymer ratio, stirring speed, volume of processing medium were optimized to maximize the entrapment. The release of salbutamol sulphate from ethyl cellulose microsphere was compared and possible release mechanism proposed. Microspheres were prepared by water in oil emulsion technique using acetonitrile/dichloromethane (1:1 ratio) solvent system. Span 80 was used as the dispersing agent and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well as compatibility by infrared spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffractometry and scanning electron microscopy (SEM). The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 55.7 - 76.6 % of entrapment and release was extended up to 10 h. Various processing and formulation parameters such as drug/polymer ratio, stirring speed, volume of processing medium, etc. significantly affect the drug release from the microspheres. The best/fit release kinetics was achieved with Higuchi plot followed by zero order and first order. The release of salbutamol sulphate was influenced by altering the drug to polymer ratio and the drug release was found to be diffusion controlled.

Design and Evaluation of Salbutamol Sulphate Transdermal Delivery System

In the present study, transdermal formulations containing salbutamol sulphate (SS) using a hydroxypropyl methylcellulose (HPMC) as a hydrophilic matrix type films with different concentrations of plasticizers and enhancers such as polyethylene glycol- 400(PEG) propylene glycol (PG). glycerine (GL), and Tween.-80 were prepared by solvent evaporation technique. All the prepared formulations were evaluated for their drug content, film thickness, in vitro release and in vitro permcation through rabbit skin into phosphate buffer pH 5.8. Results showed that the proper HPMC concentration of 4%w/v_produced suitable film thickness and controlled drug release compared to the other tested concentrations. Also, HPMC matrices containing PTG and PG revealed an optimal controlled drug release within 6 hours where those matrices containing GL and Tween-80 showed the highest retardation of drug release. Therefore, the most satisfactory controlled release of SS was obtained from the matrices containing PEG and PG of 10 and 15% w/w of polymer. AIso, their flexibility characteristics make them easier for removal from the glass substrate and more convenient for evaluation. Further in vitro permeation of SS from the selected HPMC films plasticized with PEG of 10.15 and 20°. w/w of polymer using rabbit skin as biological membrane was evaluated to give an idea of the drug permeation through the human Skin. It was found that 44.76, and 78.43 percentages of SS were permeated after 6 hours, respectively.

Modified push–pull osmotic system for simultaneous delivery of theophylline and salbutamol: development and in vitro characterization

An oral osmotic system which can deliver theophylline and salbutamol sulphate simultaneously for extended period of time was developed and characterized in a view to reduce the problems associated with the multidrug therapy of asthma. Simple controlled porosity osmotic pump contained both drugs (in freely soluble form) did not provide satisfactory extended release of theophylline. A modified two-layered, push–pull osmotic system was developed by using the basic designs of various oral osmotic pumps, such as controlled porosity osmotic pump (CPOP), elementary osmotic pump (EOP) and push–pull osmotic pump (PPOP). Scanning electron microscopy of cellulose acetate coating membrane after dissolution revealed that 25% (w/w) of sorbitol can be used as an optimized concentration of pore forming agent with 25% (w/w) of plasticizer, which was kept constant. Formulations were initially developed for theophylline and the release was optimized by using two different soluble forms of theophylline with varying amount of hydrophilic polymer mixture in upper layer and polyethylene oxide (expandable hydrogel) in lower layer. Further, the release of salbutamol sulphate was optimized by keeping the drug in upper or lower layer or both layers. In vitro release studies showed satisfactory controlled release profiles of both drugs. The release profiles of both drug statistically compared with respective marketed controlled release formulations. An optimized system was selected to study the effect of concentration of pore forming agent and orifice diameter on the release of both drugs.

Development and biopharmaceutical evaluations of a new press-coated prolonged-release salbutamol sulphate tablet in man

The aim of the study described was to develop prolonged-release press-coated tablets of salbutamol sulphate from which drug release would increase with time. The bioavailability of the formulation considered best was then studied in man. The tablets, each consisting of a core and a coat, were prepared using a compression-coating technique. Salbutamol sulphate was divided between the core and the coat in the ratio 2:1 or 1 : 2. Different viscosity grades and amounts of hydroxypropylmethylcellulose (HPMC) were used in the coat. When HPMC K100 was used, release of salbutamol sulphate from tablets with 2/3 of the drug in the core increased with time. The release patterns obtained with 1/3 of the drug in the core were biphasic. With other HPMC grades, the release patterns were best described by zero-order kinetics with 2/3 of the drug in the core and square-root-of-time kinetics with 1/3 of the drug in the core. For all formulations, an increase in the amount of HPMC decreased drug release rate. In man the only statistically significant difference in bioavailability parameters between the test formulation and the commercial reference preparation related to C max values.