Aquesons Films Coating Stuied of Sustabined Release Niciotine Acid Fellets: An In-Vitro Evalutiion

Abstract

Numerous batches of nicotinic acid (niacin) pellets were coated to determine the optimum level of Surelease® coating which would exhibit in-vitro release patterns suitable for BID dosing. Various levels of Surelease, with and without the incorporation of a hydrophilic material, were studied. It was expected that a significantly high level of Surelease would be needed to obtain the desired in-vitro dissolution release rate for the water soluble drug. However, a coating level of 1.2% Surelease coating was found to have an in-vitro dissolution profile approximating that of a BID product. Scanning electron microscopic examination has shown that the surface of coating is smooth and uniform with the coating thickness of about 2 μm. The 2 months stability data showed no significant changes in the dissolution profiles.     

In-Vitro Release of Acetaminophen from Sodium Alginate Controlled Release Pellets

Abstract

The production of spheres loaded with acetaminophen by the cross linking technique was achieved. The hydrophilic polymer sodium alginate which gels in presence of a cross linking ion was used as a matrix for the spheres production. Two processing variables were studied. The drug load in the formula which varied from 5% w/v to 20% w/v, and the cross linking agents used; calcium chloride, calcium acetate, and aluminum sulfate. Also the effects of the dissolution medium and the rotational speed of the dissolution apparatus on drug release were investigated. Spheres were compacted into 450 mg tablets without the aid of excipients. The drug release from spheres containing 20% w/v drug was 90% after 6 hours, while the drug release from compacts of these spheres was 90% after 12 hours. The mechanism of drug release from spheres and compacts containing 20% w/v drug and prepared with 5% w/v cross linking material     

In-Vitro Release of Acetaminophen from Sodium Alginate Controlled Release Pellets

The production of spheres loaded with acetaminophen by the cross linking technique was achieved. The hydrophilic polymer sodium alginate which gels in presence of a cross linking ion was used as a matrix for the spheres production. Two processing variables were studied. The drug load in the formula which varied from 5% w/v to 20% w/v, and the cross linking agents used; calcium chloride, calcium acetate, and aluminum sulfate. Also the effects of the dissolution medium and the rotational speed of the dissolution apparatus on drug release were investigated. Spheres were compacted into 450 mg tablets without the aid of excipients. The drug release from spheres containing 20% w/v drug was 90% after 6 hours, while the drug release from compacts of these spheres was 90% after 12 hours. The mechanism of drug release from spheres and compacts containing 20% w/v drug and prepared with 5% w/v cross linking material     

Pharmacokinetic and In-Vitro Characteristics of Sustained Release Verapamil Products

The in-vitro dissolution and in-vivo pharmacokinetics of two marketed sustained release formulations, Verelan (V) and Isoptin SR (ISR), were compared. The effect of food on V was also examined in a separate study with conventional Isoptin (I) as a reference. Both sustained release preparations had extended dissolution profiles with 50% release times (T50%) of 4 hours for ISR and 8 hours for V. The extended in-vitro profile of V versus ISR was confirmed in-vivo with a Tmax of 7.3 hours compared to 5.0 hours, a Cmax of 114.3 compared to 171.0 and a peak to trough ratio of 3.8 compared to 10.1 for V and ISR respectively. In a second pharmacokinetic study the rate and extent of absorption of verapamil from V was shown to be unaffected by food.     

In-Vitro Release and In-Vivo Availability of Chloro-Quine Phosphate Formulated Suppositories

Abstract

Chloroquine phosphate suppositories were formulated using witepsol H15 as a model base. The physicomechanical properties of the prepared suppositories were studied. In-vitro drug release as well as in-vivo availability were determined and compared with those from commercial tablets containing the same dose of the drug (250 mg). In addition, the effect of pH of the different segments of GIT on the partition coefficient of the drug was tested

Results revealed that formulated suppositories exhibit good mechanical properties as well as high release characteristics. Volunteers received suppositories showed urine peak level after 2 hrs while with those administered the tablets the peak was reached after 3 hrs. The total amounts released were 60% and 48% from the administered dose in case of suppositories and tablets respectively. The higher bioavailability of the medicament after rectal therapy is explained on the basis of the partition coefficient data. The obtained values were 0.667, 0.941 and 5.333 at pH 1.2, 6.8 and 7.4 respectively. Volunteers used the formulated suppositories did not suffer from any GI irritation which is accompanying the oral administration of the drug. The proposed formula had no irritating effect on the rectum     

Medicament Release From Ointment Bases: V. Naproxen In-Vitro Release and In-Vivo Percutaneous Absorption In Rabbits

The in- vitro release of Naproxen from various ointment bases, including a water-washable base with the drug in the water phase (I) and the drug in the oil phase (II), a hydrophilic base with the drug in the water phase (III), and the drug in the oil phase (IV), and an anhydrous ointment (V), a gel (VI) and a modified University of California (U .C .H.) base (VII) were studied. In addition, the effects of various additives (urea, ethanol, dimethyl sulfoxide and polyethylene glycol-400) on the release of Naproxen from formulations (I) and (II) were determined. Low concentrations of urea and ethanol in the formulations increased the release of the drug from both these bases, however, higher concentrations adversely affected the release of the drug. While dimethyl sulfoxide (DMSO) had no significant effect on the drug release, the inclusion of polyethylene glycol-400 in both bases decreased the release of Naproxen.

The percutaneous absorption of Naproxen from the waterwashable base (drug in the oil phase) and hydrophilic base (drug in the oil phase) were studied by applying the ointments on rabbit's skin. It was observed that the bioavailability of Naproxen from the hydrophilic base was slightly greater than that from the water-washable base, and that DMSO had no effect in enhancing the in-vivo release of Naproxen from the ointments evaluated. Using the in-vivo data, the absorption and elimination rate constants, the half-life and AUC were calculated.     

Preparation and In-Vitro Evaluation of Prolonged Release Tablets of Pheniramine Aminosalicylate

Prolonged release tablets of pheniramine aminosalicylate were prepared from co-precipitates of the drug in different types of Eudragit. The hardness of the tablet had a pronounced effect on the release rate of the drug. Tablets (500 mg, hardness 13 kg) and 375 mg tablets (hardness 6.5 kg) prepared from the co-precipitates containing 15% of the drug in Eudragit L 100, and 20% of the drug in Eudragit S 100 respectively, showed release rate patterns that were in agreement with Lang primary requirements for drug release from sustained release tablets.

Tablets (500 mg) prepared from the co-precipitates containing 15% of the drug in Eudragit L 100 or Eudragit S 100 and 375 mg tablets containing 20% of the drug in Eudragit S 100 showed release rate patterns that were best described by Higuchi equation, indicating that a diffusion controlled mechanism was mainly operative.     

Development and In-Vitro Evaluation of a Multiparticulate Sustained Release Theophylline Formulation

A multiparticulate sustained release formulation of theophylline was developed and evaluated in-vitro. The formulation comprised spherical pellets of high drug loading, coated with a rate controlling membrane. The pellets were prepared using an extrusion spheronisation method, whilst coating was performed with an aqueous dispersion of ethylcellulose using a fluidized bed coating technique. When ethylcellulose was used alone as the coating polymer, the drug release profile was unsatisfactory, but could be improved by incorporating a coating additive. Several additives were evaluated and methylcellulose of high Viscosity grade was found most satisfactory. The in-vitro theophylline release was relatively linear and pH independent, and could be varied in a predictable manner by manipulating the coat thickness. In addition, when the coated pellets were subjected to additional thermal treatment, the drug release was stable after storage for one year.     

Mucosal Delivery of Progestational Steroids from a Controlled Release Device: In-Vitro/In-Vivo Relationships

The mucosal delivery of progestational steroids from a model controlled release device was studied using female New Zealand White rabbits as the animal model. A controlled release device was developed which was suitable for nasal, rectal and vaginal application. The in-vitro permeation and in-vivo absorption of progesterone from the model controlled release device was investigated through the nasal, rectal and vaginal mucosa. The influence of penetrant hydrophilicity on the in-vitro permeation and in-vivo absorption from the controlled release device was also investigated using the mono-hydroxy, di-hydroxy and tri-hydroxy derivatives of progesterone. The results indicate that the nasal route demonstrates a significantly higher rate of in-vitro permeation and extent of in-vivo absorption than the rectal and vaginal mucosa. The in-vitro permeation rates and steady-state plasma concentrations achieved from the device tend to decrease with increasing penetrant hydrophilicity. A linear in-vitro/in-vivo correlation was obtained for all the mucosa studied. The slope of the relationship between the in-vitro and in-vivo data was similar for the rectal and vaginal mucosa. The results of this investigation agree with the results of a previous investigation with a solution formulation, and suggest that the hydrodynamic and/or membrane barrier properties of the nasal mucosa may from that of the rectal and vaginal mucosa.     

Mucosal Delivery of Progestational Steroids from a Controlled Release Device: In-Vitro/In-Vivo Relationships

Abstract

The mucosal delivery of progestational steroids from a model controlled release device was studied using female New Zealand White rabbits as the animal model. A controlled release device was developed which was suitable for nasal, rectal and vaginal application. The in-vitro permeation and in-vivo absorption of progesterone from the model controlled release device was investigated through the nasal, rectal and vaginal mucosa. The influence of penetrant hydrophilicity on the in-vitro permeation and in-vivo absorption from the controlled release device was also investigated using the mono-hydroxy, di-hydroxy and tri-hydroxy derivatives of progesterone. The results indicate that the nasal route demonstrates a significantly higher rate of in-vitro permeation and extent of in-vivo absorption than the rectal and vaginal mucosa. The in-vitro permeation rates and steady-state plasma concentrations achieved from the device tend to decrease with increasing penetrant hydrophilicity. A linear in-vitro/in-vivo correlation was obtained for all the mucosa studied. The slope of the relationship between the in-vitro and in-vivo data was similar for the rectal and vaginal mucosa. The results of this investigation agree with the results of a previous investigation with a solution formulation, and suggest that the hydrodynamic and/or membrane barrier properties of the nasal mucosa may from that of the rectal and vaginal mucosa.     

Piroxicam Release from Dermatological Base: In-Vitro Studies using Cellulose Membrane and Hairless Mouse Skin

Abstract

Piroxicam is one of the most potent non-steroidal, anti-inflammatory agents which also exhibits antipyretic activity. Piroxicam is well absorbed following the oral administration, however, its use has been associated with a number of gastro-intestinal disorders including bleeding and ulceration. To overcome these side effects, this study was undertaken to develop diadermatic dosage form using various polymeric gel and ointment bases containing 1% piroxicam were prepared to study the in-vitro release of the drug. Also, a series of additive ingredients, such as, alcohol USP, polyethylene glycol-400 and dimethyl sulfoxide (DMSO) were incorporated in these formulations at various concentration levels to evaluate their effects on drug release. The general rank order for the in-vitro drug release from all the bases evaluated was: gel base > hydrophillic base > emulsion base. In general, additives had little or no effect in enhancing the drug release from these bases. The in-vitro release data were treated with various kinetic principles to assess the relevant parameters, such as, diffusion coefficient, permeability coefficient, partition coefficient, zero order and first order rate constants. Among the formulations evaluated, the gel base containing (DMSO) gave the best in-vitro drug release both through the cellulose membrane and the hairless mouse skin.     

Preparation, Characterization and In-Vitro Release Kinetics of Salbutamol Sulphate Loaded Albumin Microspheres

Salbutamol sulphate loaded Bovine serum albumin microspheres were prepared by heat denaturation method. The effects of such preparation conditions as denaturation temperature, denaturation time, protein concentration and phase volume ratio on the extent of drug loading, size and size distribution and drug release were studied. An increase in protein concentration from 5% w/v to 15% w/v increased the mean particle size from 8.5 μm to 16.6 μm and decreased the drug loading from 46% w/w to 18% w/w. A decrease in the phase volume ratio substantially lowered mean particle size and size distribution. An increase in the severity of denaturaion conditions lowered both the drug incorporated and drug released. The kinetics of drug release from microspheres were compared to the theoretical models of Higuchi diffusional release and first order release. Both the models gave an adequate fit to the data. Scanning electron microscopy revealed that the dummy microspheres are spherical with smooth surfaces. As the drug-protein ratio increased, the microspheres exhibited rough surfaces showing the presence of drug crystals.     

Preparation and In-Vitro Evaluation of A Controlled Release Drug Delivery System of Theophylline Using An Aqueous Acrylic Resin Dispersion.

Abstract

Eudragit® E30D was utilized in conjunction with talc and xanthan gum to coat theophylline granules via a Wurster-type air suspension column. Since the resin is extremely tacky and cannot be used alone as a coating formulation, different amounts of talc and xanthan gum were incorporated into the Eudragit® E30D suspension to allow for coating of theophylline granules. The release profile of theophylline from the coated granules was found to be dependent on the ratio of the additives to the resin used in the coating suspension as well as on the coating level applied to the final product. A sample of theophylline granules coated with a film-coating suspension containing 1.5:1.0: :Talc: Eudragit® E30D resin (calculated on dry basis) exhibited a zero order release profile. However, the in-vitro release rates of this formulation decreased on storage. As the ratio of talc and Eudragit® E30D was changed to 1:1, the coated theophylline granules showed a release profile that remained unchanged even after exposure at room temperature, 30° C and 40° C for three months. A stable theophylline formulation was achieved by curing the coated product at 40°C for 24 hours.     

Hot-Melt Coating: Water Sorption Behavior of Excipient Films

Hot-melt coating allows encapsulation of water-labile, drug-laden substrates to form a barrier that resists moisture ingress. To understand the interaction of water with excipients that can form moisture-protective coatings, sorption behavior of films of lipidic (glyceryl behenate) and polymeric (polyvinyl alcohol) coating excipients was investigated. A simple and rapid method using a new, fully automated instrumental technique to investigate the sorption/desorption behavior of excipient films is reported. Further, the influence of temperature and film thickness on the sorption behavior of films is examined. Both excipient films displayed sorption isotherms that were classified as type III and demonstrated hysteresis during desorption. The sorption data for both films did not follow the Langmuir model, and the BET model could only be used restrictively. The GAB model fitted the sorption data at all conditions and over the entire range of water activity studied. The ability of the Young and Nelson model to explain the hysteresis behavior, from analytical and mechanistic perspectives, is evaluated. Temperature and film thickness were found to profoundly influence the nature of moisture interaction and distribution of moisture in the excipient films. An Arrhenius-type relationship was observed between equilibrium moisture content of excipient films and temperature at constant water activity.     

Diadermatic Dose Forms Of Testosterone: In-Vitro Release Studies and in-Vivo Absorption In A Human Male

Abstract

The study was undertaken to evaluate the in-vitro release of testosterone from various topical bases and to screen formulations with the optimum drug release for in-vivo evaluations in a human male. Several diadermatic bases containing 2% testosterone were prepared and studied for the in-vitro release of drug through the cellulose membrane using the diffusion methods. Also, additive ingredients such as, ethanol, polyethylene glycol-400, and dimethylsulfoxide (DMSO) at various concentration levels were included in these formulations to study their effects on the release rate of the drug. The general rank order of testosterone release from these bases was: water-washable base > hydrophilic base > University of California Hospital Base > gel base > cream base > water-soluble base > emulsion base. Except for the water-washable base containing 15% polyethylene glycol-400, all additives had little or no effect on the drug release. The formulations with the best in-vitro drug release were selected and evaluated for in-vivo drug release in a single male volunteer. Each formulation equal to 50mg of testosterone was applied on the forearm, and following each application, 24 hour urine samples were collected and analyzed for the Urinary free testosterone and its principal metabolites, i.e. androsterone and etiocholanolone. A 50mg of oral testosterone in a plain gelatin capsule was used as the control to compare the bioavailability profiles. The ratio of urinary-free testosterone to its main metabolites was found to be (1:1) from one of the topical formulations evaluated compared to (1:20) obtained in the case of oral dose of testosterone used as the control. This suggests that more drug was able to escape the pre-systemic inactivation and resulted in the higher level of free testosterone in the body.     

Preparation and In-Vitro Evaluation of Powder Solution Tablets of Valproic Acid

Abstract

A tablet dosage form of liquid valproic acid (VPA) was formulated using powder solution technology as an alternative to the manufacturing of soft elastic gelatin capsules (SEGs). Mixing of liquid VPA with suitable adsorbents followed by blending with other excipients resulted in a non-adherent, free flowing powder. Tableting was achieved through standard direct compression. The tablets were acceptable in terms of physical properties. Film coated tablets (FCTs) and sugar coated tablets (SCTs) were also prepared. The in-vitro dissolution rates of these VPA tablets were significantly greater than that of a marketed SEG product. There was no significant change in the dissolution rates of the plain and FCTs after storage under accelerated stability conditions. Powder solution technology was a viable alternative to the commercial preparation of SEGs.     

In-Vitro Dissolution Profile and Optimization of Assay Technique for Sustained Release Vitamin C Products

Abstract

Six commercial sustained release Vitamin C products in the form of encapsulated coated pellets and compressed matrices were evaluated. A modified NF XIV procedure was used to monitor the release rate under two separate conditions. One condition involved bubbling of nitrogen gas in the extracting fluid in the bottle and displacement of air with nitrogen in the head space. The other involved no deaeration of extracting fluid with nitrogen and no displacement of air in the head space. Recovery of Vitamin C from some of the products evaluated was significantly higher, especially at higher pH of extracting fluid (pH > 4.5) using nitrogen gas. Release profiles varied significantly among the products under the conditions investigated.     

In-Vitro Release and Permeation Kinetics of Pentazociwe From Matrix-Dispersion Type Trawsdwul Drug Delivery Systw

A matrix-dispersion type Transdermal Drug Delivery System (TDS) of Pentazocine (PZ) was fabricated, using combinations of rate controlling polymers, namely Eudragits RS100 (RS), RL100 (RL), Ethylcellulose (EC) and Polyvinyl pyrrolidone (PVP), with the objective of examining the effects of formulation variables on drug-permeation profiles. In depth in-vitro drug release and skin-permeation kinetics with three different loads, and also the effects of combination of isopropyl Myristate (IPM), as permeation enhancer, were studied using male albino mice abdominal skin. The release of PZ over a 12 hour period followed Higuchi kinetics, while in-vitro mice-skin permeation of PZ followed an apparent Zero-order kinetics over a period of 24 hours.     

In-Vitro Release Kinetics of Salbutamolsulphate Microcapsules Coated with Both Eudragit Rs 100 and Eudragit RL 100

Sabutamolsulphate, a bronchodialatory drug for Asthma is encapsulated by Eudragit RS 100 and Eudragit RL 100 of varying ratios (1:1, 3:1, 1:3) using Emulsion-Solvent-Evaporation method. The experimental data obtained from the in-vitro dissolution study have been computed in the light of different kinetic models like Zero Ordr, Higuchi Matrix, First Order, Baker-Lonsdale. An extensive programming in BASIC is performed to determine the co-relation coefficient and slope for each of the functions. The diffusivity rate constant (K_BL) and diffusion coefficient (Da) have been evaluated with the help of Baker-Lonsdale Model.