Controlled Porosity Osmotic Pump Research Articles

Design and Characterization of an Osmotic Pump System for Optimal Feeding and pH Control in E. coli Culture to Increase Biomass.

Batch cultures used for various purposes, such as expression screening and recombinant protein production in laboratories, usually have some drawbacks due to the bolus addition of carbon sources, such as glucose and buffers, that lead to overflow metabolism, decreased pH, high osmolality, low biomass yield, and low protein production. This study aimed to overcome the problems of batch culture using the controlled release concept by a controlled porosity osmotic pump (CPOP) system. The CPOP was formulated with glucose as a carbon source feeding and sodium carbonate as a pH modifier in the core of the tablet that was coated with a semipermeable membrane containing cellulose acetate and polyethylene glycol (PEG) 400. The release rate was regulated with Eudragit L100 as a retardant agent in the core and PEG 400 as a pore-former agent in the coating membrane. Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) were used to elucidate compatibility between components and release mechanism, respectively. The in-vitro release of glucose and Na2CO3 studies were performed for 24 hours in a mineral culture medium (M9). Then, the effectiveness of CPOP in the growth of Escherichia coli (E. coli BL21) as a microorganism model was evaluated. Glucose consumption, changes in medium's pH, and acetate concentration as a by-product were also monitored during the bacterial growth. Fourier-transform infrared spectroscopy confirmed the compatibility between the components in the osmotic pump, and SEM elucidated the release mechanism due to in-situ delivery pores created by dissolving soluble components (PEG 400) on the coated membrane upon contact with the dissolution medium. The in-vitro release studies indicated that the osmotic pump was able to deliver glucose and sodium carbonate in a zero-order manner. The use of CPOP in E. coli (BL21) cultivation resulted in a statistically significant improvement in biomass (over 80%), maintaining the pH of the medium (above 6.8) during the exponential phase, and reducing metabolic by-product formation (acetate), compared to bolus feeding (P < 0.05). The use of CPOP, which is capable of controlled release of glucose as a carbon source and sodium carbonate as a pH modifier, can overcome the drawbacks of bolus feeding, such as decreased pH, increased acetate concentration, and low productivity. It has a good potential for commercialization.

Design, optimization, and characterization of an in-situ pore-forming system for controlled delivery of paliperidone

The purpose of the current investigation was to develop a pharmaceutical equivalent osmotic drug delivery formulation of Paliperidone (PLD) in the form of controlled porosity osmotic pump tablets (CPOT) in order to keep the drug's steady state concentration in the body. This helps to achieve the greatest therapeutic benefit with the fewest side effects. For the purpose of identifying various formulation attributes, preliminary trials were conducted. Taguchi design was used to study the influence of seven input factors namely drug to polymer ratio, polymer 1(HPMC K100 M) to polymer 2 (HPMC K15 ​M), drug to total osmogens, coating level, amount of pore former, concentration of ethyl cellulose and amount of plasticizer on dependent variable similarity factor (f2). Utilizing the Minitab 17, data analysis was done. The similarity factor (f2) was computed using the osmotic tablet reference product INVEGA®. The findings demonstrate that each of the seven independent variables significantly affects the similarity factor. For optimized batch, both core and coated tablets showed acceptable pharmaco-technical parameters. The release profile of the optimized batch tablets was found to be similar to that of reference product with good zero-order release pattern. Drug release was observed through the channels formed by in-situ pores on tablet surface performed using SEM. From the results it can be concluded that prepared CPOT of PLD was found pharmaceutical equivalent with commercial product which is cost effective and fully compliance with cGMP.

Formulation and evaluation of controlled porosity oral osmotic pump tablets of furosemide

Oedema is an abnormal accumulation of fluid in the interstitium located beneath the skin and in the cavities of the body which can cause severe pain. Furosemide has been shown to be effective and safe in patients with hypertension and/ or coronary heart disease. Osmotic pump tablets deliver the drug in an optimized manner to maintain drug concentration within the therapeutic window and minimize toxic effects. The major objective of the study was to prepare and evaluate oral controlled porosity osmotic pump tablets of furosemide, to reduce the dosing frequency and thereby side effects, and to release the drug for a prolonged period in a controlled manner that is independent of pH and hydrodynamic activity. Pre-formulation studies and pre-compression parameters of tablet blends of osmotic pump tablets of furosemide were carried out. Oral-controlled porosity osmotic pump tablets of furosemide were prepared and subjected to different evaluation tests. Precompression parameters indicated that granules have a good flow property. All the formulations showed good mechanical strength. All the nine formulations showed a drug release of more than 60% in the 12th hour. Optimised formulation showed a drug release of 99.21% in 12th hr. Stability studies conducted indicate that the product is stable.

Effect of Coating Thickness and Polyethylene Glycol’s Molecular Weight on Diltiazem Hydrochloride Release from Controlled Porosity Osmotic Pump Tablets

The purpose of this research was to design CPOP tablets to achieve controlled delivery of diltiazem hydrochloride (DH) up to 12 hours, which is a water-soluble calcium channel blocker with a short biological half-life. Two batches of osmotic tablet cores were prepared, containing DH with mannitol as an osmotic agent (1: 1.5 ratio). The tablet cores formulation with 10 mm diameter achieved the required technical and mechanical specifications. Direct compression technique was used to prepare the tablet cores which were evaluated in terms of mechanical resistance and uniformity of dosage units, followed by spray film coating using cellulose acetate as a former polymer of the semipermeable membrane and polyethylene glycol (PEG) as a pore forming agent. Several molecular weights of PEG (6000, 1500 and 400) were used and coating thickness levels were obtained. In vitro drug release, morphology of coating surface and the effect of pH change on release rate were investigated. Most of the prepared formulations demonstrated a burst release at the initial stage, which could be controlled by increasing the coating thickness. Formulations with PEG400 as a pore former presented better controlled and less burst release than those containing PEG6000, PEG1500, or a mixture of PEG6000: PEG400 (1: 1), and the pH change did not affect the drug release except in the initial stage.

Effect of Cellulose Acetate (CA-398-10 NF/ EP) on Osmotically Controlled Drug Delivery System of Amitriptyline

Background: Amitriptyline hydrochloride is a Tricyclic Antidepressant (TCA) belonging to BCS class I exhibiting only 30-60% bioavailability and often coupled with poor patient compliance. The primary objective was to develop a formulation with commercial viability and to reduce dosing frequency in order to promote adherence of depressed patients to the treatment regime. The study also focused on reducing the dose of amitriptyline by controlling the release using osmotic technology; thereby reducing the side effects of amitriptyline. Methods: Controlled Porosity Osmotic Pump (CPOP) systems eliminate the need for expensive drilling processes and in turn are apt for industrial manufacturing systems where as other osmotic systems have practical limitations. Wet granulation technique was used for the formulation of CPOP tablets of amitriptyline as burst release was observed in directly compressed tablets. Screening of polymers, osmogen and weight gain were performed. Results: F6-D3 (3 % Di-butyl phthalate) with lactose as osmogen and HPMC K 35 M as polymer was optimized. The drug release from the optimized formulation was found to be independent of the effect of agitational intensity and pH. To confirm the osmotic release mechanism, the osmotic pressure of the dissolution medium was increased. The drug release decreased markedly due to an increase in osmotic pressure. Conclusion: Accelerated Stability studies were carried out in ICH certified stability chambers as per the specifications and were found to be stable. It was evident that osmotic pressure generated within the CPOP tablets along with the controlled formation of pores using Cellulose Acetate (CA-398-10 EP/ NP) was able to control the release of amitriptyline hydrochloride for 24 hours. Thus, the Oral Osmotic Drug Delivery system is a promising technology for product life-cycle strategies.

SYNCHRONOUS AND CONTROLLED CONVEYANCE OF METFORMIN HYDROCHLORIDE AND GLIPIZIDE CONTROLLED POROSITY OSMOTIC PUMP IN-VITRO QUANTIFICATION

In the current research, controlled porosity osmotic pump (CPOP) tablet is prepared by direct compression method and the tablet coating was achieved by a dip-coating process using chitosan as conveyance retardant to decrease the burst release time of Metformin HCl (MTF), sodium hydrogen carbonate as pH modifier and Hydroxy Propyl Methyl Cellulose (HPMC) E 15 LV as hydrophilic polymer to improve the appearance of Glipizide (GLZ) to pass on the blend of MTF and GLZ in a kept up and synchronized way. The prepared tablets were characterized for its release. The release data was fitted with release kinetics in order to determine order of release and release mechanism. The impact of release retardant shows that there is no blasted delivery of MTF was noticed upto 4th h and the delivery was controlled up to 24h and the delivery pace of GLZ was improved while joined with MTF and sodium bicarbonate. In conclusion, this methodology could be gainful for the treatment of diabetes mellitus Type 2 (DMT2) with improved disintegration.

Formulation development and evaluation of osmotic drug delivery system for lornoxicam

Osmotic systems are the most reliable controlled drug delivery systems and can be employed as oral drug delivery systems. Osmotic pressure is used as the driving force for these systems to release the drug in a controlled manner. Osmotic pump tablet (OPT) generally consists of a core including the drug(s), an osmotic agent, other excipients and semipermeable membrane coat. The aim of current study was to develop osmotic drug delivery system for Lornoxicam. Two different approaches were used for formulation, one was controlled porosity osmotic tablet and other was elementary osmotic tablet. The formulations were evaluated for different parameters like appearance, uniformity of weight, drug content, hardness and drug release also the effect of different osmotic agents responsible for developing the osmotic pressure such as sodium chloride and mannitol along with different concentration of pore former sorbitol were studied and comparison was made between first controlled porosity osmotic tablet which include the osmotic tablet in which coating membrane contains water soluble pore forming polymers when the membrane comes in contact with water the leaching of polymers occur thereby permitting the water inside the wall and creating the osmotic pressure to release the drug and second the elementary osmotic tablet containing osmotic agent sodium chloride coated with the rate controlling semipermeable membrane of cellulose acetate, this membrane contains an orifice of a critical size through which the drug is delivered. From the results it was found that the developed formulation the controlled porosity osmotic tablet of Lornoxicam (CPOP) was able to release the drug over 12 hrs at zero order and also the concentration of osmotic agent, level of pore former and thickness of coating membrane are responsible for controlling the release of Lornoxicam. The coating membrane was subjected to SEM analysis which showed formation of pores in the membrane. The developed controlled porosity osmotic pump tablet of lornoxicam was found to control the release for 12 hrs.

Development of leachable enalapril tablets by controlled porosity osmotic pump technique; a unique approach to enhance its sustained release effect

Development of leachable enalapril tablets by controlled porosity osmotic pump technique; a unique approach to enhance its sustained release effect

A Review of Novel Drug Delivery Controlled Porosity Osmotic Pump Tablets Therapeutic Approach and Future Trend

The review work is comprised the enhancement of bioavailability and increase therapeutic efficacy. The porous osmotic pump tablets were designed using D‐Optimal design and numerical optimization technique was applied to find out the best formulation. Another hand an osmotic pump (OP) were designed and evaluated with the aim to deliver drug in a controlled manner. Osmotic agent and pore former was considered as independent variables. Drug release rate at 2 h, 4 h, 8 h, 12 h, T50% and release exponent (n) were taken as responses. The increase in concentration of pore former and osmotic agent after a limit, changes the release was measured. The optimized formulation follows mechanism measured. The FT‐IR and DSC studies revealed that no physicochemical interaction between excipients and drug. The influence of pH and agitation intensity on the release of drug was studied and the release mechanism was through osmosis. Stability studies revealed that optimized formulation was stable. The result of D‐ Optimal design and ANOVA studies reveals that osmotic agent and pore former have significant effect on the drug release up to 12 h. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility.&#x0D; Keywords: osmotic pump, pore former, bioavailability

Evaluation of Controlled Porosity Osmotic Pump for Oral Delivery of Ketorolac

Evaluation of Controlled Porosity Osmotic Pump for Oral Delivery of Ketorolac

Development and Characterization of Controlled Porosity Osmotic Pump Tablets of Captopril

Background: The objective of the present study was to design a porous osmotic pump-based drug delivery system for the controlled release of captopril (Cap) which can maintain a constant therapeutic concentration, thus reducing dose-related side effects and dosing frequency. Methods: The study evaluated in vitro drug release for the controlled porosity osmotic pump tablet (CPOPT) of Cap. This in vitro drug release study investigated the influence of the tablet formulation variables such as the amount of mannitol, hydroxypropylmethylcellulose K4M (HPMCK4M), and polyvinyl pyrrolidone (PVP K-30) in the core and the concentration of cellulose acetate and polyethylene glycol 400 (PEG-400) in the coating solution. Results: It was found that the drug release was mostly affected by the amount of mannitol, HPMCK4M, and PVP K-30 in the core and the amount of cellulose acetate and PEG-400 in the coating solution. Conclusion: In general, the objective of the study was established by coating the core tablet containing osmotic and pore-forming agents. Therefore, the CPOPT of Cap could be a safe, effective, stable, and promising preparation in the future.

Formulation and stability studies of metformin hydrochloride in a controlled porosity osmotic pump system

Formulation and stability studies of metformin hydrochloride in a controlled porosity osmotic pump system

Leachable pegylated cellulose acetate complex: a promising approach for controlled porosity osmotic pump tablets of Captopril

The aim of the present study was to develop pegylated cellulose acetate coating layer having leachable membrane created by controlled porosity osmotic pump (CPOP) technique. Already optimized core tablets of Captopril were used for the application of CPOP. In Box–Behnken design, cellulose acetate, polyethylene glycol, and sorbitol were used as variables and %Captopril release as a response for the coating process. Formulations were characterized by weight gain, thickness of leachable membrane, content uniformity, drug release, pH, dissolution medium osmolality effect, FTIR, and stability analysis for the optimization purpose. Optimized formulation was within the pharmacopoeial limits. Observed weight gain was 4.38–6.97%, and thickness of leachable membrane was 1.24–1.47 mm. Content uniformity was found to be 91.65–99.61%. Phosphate buffer of pH 6.8 showed 86.22–92.79% drug release and the first-order release pattern. pH-independent but osmolality-dependent drug release was observed. No incompatibility between the ingredients of prepared dosage form was observed in FTIR analysis. Accelerated stability study for 6 months showed no significant change in the prepared dosage form. Conclusively, prepared CPOP tablets can be used for the controlled release of Captopril in hypertensive patients to maintain the desired drug concentration within the body for required time period.

Design and Development of Controlled Porosity Osmotic Pump Tablets of Zidovudine Using Sodium Chloride as Osmogen for the Treatment of Aids

The present study investigates the feasibility of the design and develops controlled porosity osmotic pump (CPOP) tablets to prolong the drug release of an antiretroviral drug zidovudine of 600mg once daily. Five formulations (ZS1to ZD5) were prepared by wet granulation method using various excipients. The CPOP consisted of an osmotic core coated with a micro porous membrane made up of cellulose acetate, poly ethylene glycol and sorbitol as in situ micro pore former. The prepared tablets were evaluated for pre compression parameters, post compression parameters, in vitro drug release study, Fourier Transform Infrared Spectroscopy (FTIR) study, Differential Scanning Calorimetry (DSC) study and scanning electron microscopy (SEM) study. The formulation variables such as effect of osmogen concentration, effect of pore former concentration, effect of membrane thickness of semi permeable membrane were evaluated for drug release characteristics. For the optimized formulation (ZS4) effect of osmotic pressure, effect of pH and effect of agitation intensity was evaluated. The in vitro release kinetics were analyzed for different batches by different pharmacokinetic models such as zero order, first order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell model. The result of optimized formulation releases drug up to 16 hrs in a controlled manner and follows Higuchi kinetics and which is independent of the pH and agitation intensity. The optimized formulation was found to be stable up to 3 months when tested for stability study at 40±2ºC/ 75±5% RH

Formulation of controlled porosity osmotic pump tablets containing venlafaxine hydrochloride

Formulation of controlled porosity osmotic pump tablets containing venlafaxine hydrochloride

Effect of Polyethylene Glycol on Cellulose Acetate Films Designed for Controlled Porosity Osmotic Pump Systems

This study aimed to investigate the properties of the films containing cellulose acetate and different amounts of polyethylene glycol 200 designed for controlled porosity osmotic pump systems. Polyethylene glycol 200 was used as a plasticizer and pore-forming agent and was incorporated into the cellulose acetate films at the varied concentrations. Water permeability through the films was determined based on the osmotic pump system using a device developed for this study. The film properties including polymer interaction, mechanical properties, swelling properties, thickness, porosity, polarity and morphology of the films were investigated. The amount of polyethylene glycol 200 had an effect on the film strength and the water permeability, increasing the amount resulted in greater water permeability. Scanning electron microscopy images showed that there was an increase in the number of pores in the films as the polyethylene glycol 200 content was increased. Moreover, the thickness of the films also affected the water permeation rate, increasing the thickness led to a decrease in the water permeability. This study reported additional knowledge regarding the properties and characteristics of cellulose acetate films with different proportions of polyethylene glycol 200. This could be applied to the development of a pharmaceutical formulation especially a controlled porosity osmotic pump system in the future.

Formulation and Optimization of Controlled Porosity Osmotic Pump Tablets of Lamivudine using Sodium Chloride as Osmogen for the Treatment of AIDS

Formulation and Optimization of Controlled Porosity Osmotic Pump Tablets of Lamivudine using Sodium Chloride as Osmogen for the Treatment of AIDS

DESIGN AND DEVELOPMENT OF CONTROLLED POROSITY OSMOTIC TABLETS OF GARCINIA INDICA EXTRACT

The present study deals with the development and evaluation of controlled porosity osmotic pump (CPOP) tablets containing inclusion complexes of ethanolic extract of Garcinia indica fruit rind. Wet granulation method was used for the development of core tablets. Core tablets were incorporated with different concentrations of sodium chloride as osmogen and additives. The CPOP tablets were coated with cellulose acetate as a wall forming material and HPMC acts as pore forming material in SPM. The formulated tablets were evaluated for FTIR, DSC, pre-compression parameters, post compression parameters, in vitro drug release study and scanning electron microscopy study. The optimized formulation had no significant effect on the pH and agitation intensity. SEM images revealed that no pores were found before dissolution and after dissolution had shown the porous nature of the membrane. It was found that the optimized formulation (P4) delivers a drug at a zero-order rate for 24 hours. Short term stability study at 40±2ÂoC /75±5% RH for the months on the optimized formulation indicated that there was no significant change in weight variation, % friability, drug content and in vitro drug release. Keywords: Osmotic system, cellulose acetate, pore former, controlled porosity, Garcinia indica

Electrostatic coated controlled porosity osmotic pump with ultrafine powders

In the present study, novel controlled porosity osmotic pump were formed by an electrostatic coating technology with ultrafine powders. Containing film forming polymer (cellulose acetate, CA) and pore former, ultrafine coating powders were electrostatically deposited onto the surface of osmotic pump cores with an electrostatic spray gun, followed by a curing step to allow those deposited ultrafine particles to coalesce and form a continuous coating film. Colloidal silicon dioxide was found to be efficient in increasing the flowability of the ultrafine coating powders, leading to a higher coating powder adhesion rate and more uniform coating film. Longer curing time and/or higher curing temperature resulted in a better and more continuous coating film. The results of dissolution tests and the modeling of the drug release profiles showed that the drug release from the electrostatic coated controlled porosity osmotic pump followed a zero-order drug release kinetics. A desirable drug release rate could be achieved by adjusting the coating level and/or the pore former ratio in the coating formulation.

Formulation and Optimization of Porous Osmotic Pump based Controlled release System of Ritonavir for the Treatment of HIV Infection

The current research involves the development of controlled porosity osmotic pump (CPOP) tablets of ritonavir for the treatment of HIV infection. Core tablets were prepared by wet granulation method using hydroxyl propyl methyl cellulose (HPMCE5LV) polymer, mannitol as osmogen, MCC as diluents and other additives. The CPOP tablets were coated with cellulose acetate as wall forming material, poly ethylene glycol as flux regulating agent, and sorbitol acts as pore forming material in SPM. The prepared tablets were evaluated for FTIR, DSC, pre compression parameters, post compression parameters, in vitro drug release study and scanning electron microscopy study. The optimized formulation RM5 showed 94.83% at the end of 14 hrs with zero order drug release. The difference factor (f1) and similarity factor (f2) for RM5 were observed 14.61 and 75.12 respectively. Optimized formulation did not show any significant change on the pH and agitation intensity, but it depends on osmotic pressure of dissolution media indicated that mechanism of drug release was due to osmotic pressure. SEM micrographs confirmed that no pores were found before dissolution and after dissolution had shown the porous nature of the membrane. Short term stability study at 40±2oC/75±5% RH for three months on the RM5 formulation indicated that there was no significant change weight variation, % friability, drug content and in vitro drug release.