Controlled Porosity Osmotic Pump Tablets Research Articles

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.

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.

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.
 Keywords: osmotic pump, pore former, bioavailability

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.

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

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

Formulation and Evaluation of Controlled Porosity Osmotic Pump Tablets for Oral Delivery of Stavudine

The current research was designed to develop controlled porosity osmotic pump (CPOP) tablets of stavudine a nucleoside reverse transcriptase inhibitor for the treatment of acquired immune deficiency syndrome (AIDS) Wet granulation method was adopted for the development of tablet of 80 mg dose of stavudine for once daily. The formulated tablets were evaluated for pre compression parameters, post compression parameters, in vitro dissolution study and scanning electron microscopy study. The in vitro release kinetics were analyzed for different batches by different pharmacokinetic models such as zero order, first order, Higuchi, Korsmeyer Peppas and Hixon Crowell model. The results of optimized formulation releases drug up to 18 h in a controlled manner and follow Higuchi kinetics and which is independent of the pH and agitation intensity. Short term stability study at 40±2oC/75±5% RH for three months was carried out and observed that the optimized formulation did not show any significant changes in hardness, friability, weight variation, drug content, in vitro dissolution study etc.

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.

FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC PUMP TABLETS FOR ZIDOVUDINE AND LAMIVUDINE COMBINATION USING FRUCTOSE AS OSMOGEN

The present study deals with the development and evaluation of controlled porosity osmotic pump (CPOP) tablets of zidovudine-lamivudine. Wet granulation method was used for the development of core tablets. Core tablets were incorporated with HPMCE5 LV polymer, different concentrations of fructose as osmogen and additives. The CPOP tablets were coated with cellulose acetate as a wall forming material, polyethylene glycol as flux regulating agent, and sorbitol 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 p H and agitation intensity, but depends on the osmotic pressure of dissolution media indicated that mechanism of drug release. SEM images revealed 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 the months on the CF4 formulation indicated that there was no significant change weight variation, % friability, drug content and in vitro drug release. Keywords: HPMCE5LV, wet granulation, CPOP, in vitro drug release, stability study .

Controlled Porosity Osmotic Pump Tablets of Zidovudine and Lamivudine Combination: Optimization and Characterization

Controlled Porosity Osmotic Pump Tablets of Zidovudine and Lamivudine Combination: Optimization and Characterization

Development and Evaluation of Controlled Porosity Osmotic Pump Tablets for Zidovudine and Lamivudine Combination

The present work was aimed to develop and evaluate controlled porosity osmotic pump (CPOP) tablets of zidovudine-lamivudine combination for the treatment of AIDS. The tablets were prepared by wet granulation method incorporating drug, various excipients, controlled release polymer hydroxyl propyl methyl cellulose (HPMCE5M LV) and osmogen (Mannitol) in the core. The CPOP tablets consist of an osmotic core coated with a micro porous membrane made up of cellulose acetate (CA) which is incorporated with sorbitol as porogen. Prior to compression the prepared granules were evaluated for pre compression parameters such as angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. After compression the prepared granules were evaluated for thickness, coat thickness, hardness, weight variation, friability, drug content, diameter, in vitro drug release study and scanning electron microscopy (SEM) study. The release kinetics for different formulations were analyzed using zero order model equation, first order model equation, Higuchi model equation, Korsmeyer Peppas model equation and Hixson-Crowell equation. The optimized formulation of drug release was independent of pH, agitation intensity, but dependent on the osmotic pressure of the release media. FTIR and DSC study revealed that there was no interaction between drug and excipients. Formulations subjected to stability testing (at 40±2oC/75±5% RH) as per ICH guidelines for three months indicated stability with no significant changes in thickness, hardness, weight variation, friability, drug content and dissolution profiles.

Development and Evaluation of Controlled Release Formulation of Zidovudine Based on Microporous Osmotic Tablet Technology Using Fructose as Osmogen

The present work was aimed to develop and evaluate controlled porosity osmotic pump (CPOP) tablets of an anti HIV drug zidovudine to provide a uniform concentration of drug at absorption site. The formulations were prepared by wet granulation method using drug, various excipients, controlled release polymer hydroxylpropylmethyl cellulose(HPMCE5M LV) and osmogen (Fructose).The CPOP tablets consist of an osmotic core coated with a micro porous membrane made up of cellulose acetate(CA) which is incorporated with sorbitol as porogen. Prior to compression the prepared granules were evaluated for pre compression parameters such as angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. After compression the prepared granules were evaluated for thickness, coat thickness, hardness, weight variation, friability, drug content, diameter, in vitro drug release study and scanning electron microscopy (SEM) study. The release kinetics for different formulations were analyzed using zero order model equation, first order model equation, Higuchi model equation, Korsmeyer Peppas model equation and Hixson-Crowell equation. The optimized formulation of drug release was independent of pH, agitation intensity, but dependent on the osmotic pressure of the release media. Based on the in vitro dissolution profile optimized formulation ZF4 exhibited Fickian transport mechanism with a drug release of 97.83% in 16 hrs. FTIR and DSC study revealed that there was no interaction between drug and excipients. Formulations subjected to stability testing (at 40±2oC/75±5% RH) as per ICH guidelines for three months indicated stability with no significant changes in thickness, hardness, weight variation, friability drug content and dissolution profiles.

CONTROLLED POROSITY OSMOTIC TABLET OF ATENOLOL: IN-VITRO AND IN-VIVO EVALUATION

The aim of the present study was to design a controlled porosity osmotic pump tablet of atenolol. The controlled porosity osmotic pump tablet contains pore-forming water-soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a microporous structure. The dosage regimen of atenolol is 25-mg tablet 2 to 3 times a day. The plasma half-life ranges from ~6 to 7 hours. Hence, Atenolol was chosen as a model drug with an aim to develop a controlled release system for a period of 12 hours. The effect of different formulation variables, namely, ratio of drug to osmogent and level of pore former on the in vitro release was studied by applying a full 3 2 factorial design. Cellulose acetate (CA) was used as a semipermeable membrane. It was found that drug release was directly related to the amount of osmogent and level of pore former. In-vivo study was performed in rabbits and various parameters C max , t max , AUC, AUMC and MRT were calculated and compared with that of marketed conventional tablet. The optimized formulation was subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and formulation was stable after a 3 month study.

A Review on Drug Category Suitable for Monolithic Osmotic Tablet

Conventional drug delivery systems have little control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable controlled drug delivery systems and could be employed as oral drug delivery systems. The present review is concerned with the study of drug release systems which are tablets coated with walls of controlled porosity. When these systems are exposed to water, low levels of water soluble additive is leached from polymeric material i.e. semi permeable membrane and drug releases in a controlled manner over an extended period of time. Drug delivery from this system is not influenced by the different physiological factors within the gut lumen and the release characteristics can be predicted easily from the known properties of the drug and the dosage form. In this paper, various types of osmotic ally controlled drug delivery systems and the basic components of controlled porosity osmotic pump tablets have been discussed briefly.