Effect of excipient and processing variables on adhesive properties and release profile of pentoxifylline from mucoadhesive tablets

The bioavailability and onset of action of drugs with high first-pass metabolism can be significantly improved by administration via the sublingual route. The objective of this study was to evaluate the effect of polymer type and tablet compaction parameters on the adhesive properties and drug release profile from mucoadhesive sublingual tablet formulations. Pentoxifylline was selected as the model drug because it has poor oral bioavailability due to extensive first-pass metabolism. Two polymers known to possess mucoadhesive properties, carbomer and hydroxypropyl methyl cellulose (HPMC), were used to prepare the formulations. Tablets were prepared by using direct compression technique and evaluated for in vitro dissolution, drug-excipient interactions, and adhesive properties. In general, there was a decrease in the rate of drug release with an increase in the concentration of polymers. No drug-excipient interactions were evident from differential scanning calorimetry or high-performance liquid chromatography analysis. For the formulations containing HPMC, the force of mucoadhesion increased with an increase in the concentration of polymer; however, for carbomer formulations, no such correlation was observed. Force of mucoadhesion decreased as a function of hydration time in both of the polymers.     

Formulation and Evaluation of Mucoadhesive Tablets Containing Eugenol for the Treatment of Periodontal Diseases

Eugenol is the principle chemical constituent of clove oil and has been used to cure dental problems for ages. Eugenol is an integral part of the dentist's kit due to its analgesic, local anesthetic, anti‐;inflammatory, and antibacterial effects. It is used in the form of a paste or mixture as dental cement, filler, and restorative material. This study reports the development and evaluation of controlled‐release mucoadhesive tablets for gingival application, containing eugenol, which are prepared by taking carbopol 934 P and Hydroxypropyl methylcellulose (HPMC) K4M in the ratio of 1:2, 1:1, and 2:1. Incorporation of eugenol (10 mg) in a mucoadhesive formulation provides controlled release for a period of 8 hours, which is advantageous over conventional use. In vitro mucoadhesion measured as detachment force in grams and the formulations show good correlation in vivo. The release study indicates that increase in carbopol increases the release rate of eugenol from the formulation whereas HPMC retards it. Increased in vitro bioadhesion is related to HPMC content of the formulation. The release kinetics of eugenol in vitro correlates with the in vivo results. This indicates the increased potential of eugenol as antibacterial, local analgesic, and anaesthetic treatment.     

Investigation of Hypromellose Particle Size Effects on Drug Release from Sustained Release Hydrophilic Matrix Tablets

Selected combinations of six model drugs and four hypromellose (USP 2208) viscosity grades were studied utilizing direct compression and in vitro dissolution testing. Experimental HPMC samples with differing particle size distributions (coarse, fine, narrow, bimodal) were generated by sieving. For some formulations, the impact of HPMC particle size changes was characterized by faster drug release and an apparent shift in drug release mechanism when less than 50% of the HPMC passed through a 230 mesh (63 μm) screen. Within the ranges studied, drug release from other formulations appeared to be unaffected by HPMC particle size changes.     

Design and Evaluation In Vitro of Controlled Release Mucoadhesive Tablets Containing Chlorhexidine

ABSTRACT

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity.

Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa.

Similar tests have also been carried out on a commercial product, Corsodyl gel^®, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.     

Directly Compressed Mini Matrix Tablets Containing Ibuprofen: Preparation and Evaluation of Sustained Release

ABSTRACT

Directly compressed mini tablets were produced containing either hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) as release controlling agent. The dynamics of water uptake and erosion degree of polymer were investigated. By changing the polymer concentration, the ibuprofen release was modified. In identical quantities, EC produced a greater sustaining release effect than HPMC. Different grades of viscosity of HPMC did not modify ibuprofen release. For EC formulations, the contribution of diffusion was predominant in the ibuprofen release process. For HPMC preparations, the drug release approached zero-order during a period of 8 h. For comparative purposes, tablets with 10 mm diameter were produced.     

Effect of Formulation Composition on the Properties of Controlled Release Tablets Prepared by Roller Compaction

This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled‐release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t₇₀ values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t₇₀ data and gave an adjusted r‐square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and develop more robust processes.     

The Effect of Processing Variables on the Release of Ibuprofen and Caffeine from Controlled-Release Nonswellable Core-in-Cup Compressed Tablets

Abstract

An aqueous soluble polymer such as hydroxypropyl methylcellulose (HPMC), which is widely used in oral sustained-release drug delivery systems, swells when it comes into contact with an aqueous environment. In core-in-cup systems the swelling of the HPMC splits open the cup portion of the tablet. This study investigated the use of acacia, tragacanth, polyethylene glycol 6000 (PEG 6000), and hydroxyethyl-cellulose (HEC) as possible alternatives to the use of HPMC to control the release of caffeine (soluble) and ibuprofen (insoluble) from core-in-cup compressed tablets. It also investigated the possibility of producing a core-in-cup system that had the ability to release caffeine and ibuprofen for a maximum time of constant release of 8-12 hr. A preliminary study revealed that acacia was most effective for the release of caffeine from the core-in-cup compressed tablets, and that PEG 6000 was most effective for the release of ibuprofen from the core-in-cup compressed tablets. On further investigation it was found that by means of adjusting the hardness of compression and the concentration of polymers used, it was possible to formulate a core-in-cup system that could release drug at a constant rate from the core-in-cup compressed tablets for 8 to 12 hr.     

The Effect of Processing Variables on the Release of Ibuprofen and Caffeine from Controlled-Release Nonswellable Core-in-Cup Compressed Tablets

An aqueous soluble polymer such as hydroxypropyl methylcellulose (HPMC), which is widely used in oral sustained-release drug delivery systems, swells when it comes into contact with an aqueous environment. In core-in-cup systems the swelling of the HPMC splits open the cup portion of the tablet. This study investigated the use of acacia, tragacanth, polyethylene glycol 6000 (PEG 6000), and hydroxyethyl-cellulose (HEC) as possible alternatives to the use of HPMC to control the release of caffeine (soluble) and ibuprofen (insoluble) from core-in-cup compressed tablets. It also investigated the possibility of producing a core-in-cup system that had the ability to release caffeine and ibuprofen for a maximum time of constant release of 8-12 hr. A preliminary study revealed that acacia was most effective for the release of caffeine from the core-in-cup compressed tablets, and that PEG 6000 was most effective for the release of ibuprofen from the core-in-cup compressed tablets. On further investigation it was found that by means of adjusting the hardness of compression and the concentration of polymers used, it was possible to formulate a core-in-cup system that could release drug at a constant rate from the core-in-cup compressed tablets for 8 to 12 hr.     

Role of Cellulose Ether Polymers on Ibuprofen Release from Matrix Tablets

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and β-cyclodextrin (β-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE_{20 h}), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models—Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.     

The Effect of Excipient Solubility on the in-vitro and in-vivo Properties of Bendrofluazide Tablets 5 MG

SUMMARY

TaRblets containing bendrofluazide 5 mg have been prepared at 190, 220 and 290 MNm^-2 using four different excipients; sorbitol, lactose, calcium orthophosphate and calcium hydrogen orthophosphate. The solubilities in water of the excipients were respectively 70, 17.8, 0.03 and 0.01% W/W. Granules prepared under identical conditions were found to have moisture contents of about 3% W/W. All the four excipients were found to be equally effective in producing minimal tablet to tablet weight variation. Tablet hardness was governed by the intrinsic nature of the excipient and for all diluents an increase in compressional force produced an increase in tablet hardness. However, the size of this hardness increase varied markedly dependent on the excipient. Disintegration time and the nature of the disintegrating process varied greatly with the excipient. Generally, decreasing the solubility of the diluent decreased the disintegration time, but the pattern was complicated by the effect of compaction pressure which produced marked disintegration time differences with some excipients but not with others. No correlation was found between disintegration time and dissolution rate. However changing the excipient greatly affected the dissolution rates of the tablets in some cases by as much as 600%. Disintegration time was found to be no indicator of dissolution performance. In-vivo assessment of the tablets demonstrated that there was a direct correlation between in-vivo activity, measured as initial micturation rate, with bendro-fluazide dissolution. In general the study showed that by changing the diluent, marked differences in the in-vivo and in-vitro properties of the bendrofluazide tablets could be demonstrated and that these differences were more marked using very soluble excipients. The best excipients were found to be calcium orthophosphate and calcium hydrogen orthophosphate. Sorbitol was found to be the least useful as a tablet diluent.     

Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Abstract

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

活性炭对薄荷醇的封装及热释放性能影响

目的 研究活性炭对薄荷醇的封装和热释放性能影响,为活性炭用于加热不燃烧烟草制品的加香提供依据。方法 利用红外光谱(ATR–FTIR)、热重分析(TGA)和扫描电镜(SEM)分析活性炭对薄荷醇的封装性能,并采用热裂解气相色谱/质谱联用法(Py–GC/MS)分析350 ℃温度下活性炭中薄荷醇的热释放性能。结果 活性炭表面有众多的小孔,对薄荷醇有强的封装性能。薄荷醇被活性炭封装后,热稳定性明显提高,最大挥发峰从195 ℃提高到251 ℃,薄荷醇在350 ℃温度下热裂解产物组分少,主产物仍然是薄荷醇,相对质量分数为82.879%。结论 活性炭能够有效封装薄荷醇,延缓其释放速度,达到保香的效果。在加热不燃烧烟草制品的温和加热状态下,活性炭封装的薄荷醇具有良好的热稳定性和可释放性,活性炭可以作为薄荷醇的封装剂用在加热不燃烧烟草制品中。     

Effect of Sodium Bicarbonate on the Properties of Metronidazole Floating Matrix Tablets

The effect of sodium bicarbonate (SB) on the swelling behavior and the sustained release of floating systems was studied with varied proportions of this excipient and metronidazole. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. Under in vitro dissolution conditions, the addition of SB to metronidazole sustained-release tablets modifies the matrix hydration volume, increasing at the beginning, reaching a maximum, and then declining. Pure Carbopol matrices show a rapid hydration with a limited further effect of the SB and metronidazole loads. Methocel show a significant increase of the apparent hydration volume due to SB addition with no further notable change due to metronidazole load. Increasing the metronidazole load reduces the floating time of Carbopol matrices while no effect on Methocel matrices could be observed within 8 hours dissolution. Matrices show increasing release constant values (k) as the metronidazole load increases. Methocel matrices release the drug 10% to 15% faster than Carbopol matrices. SB increases the cumulative amount of drug released from Methocel but not that releasing from Carbopol. These results are attributed to the intrinsic polymer properties, the barrier effect of CO₂ bubbles, and the matrix volume expansion produced after addition of SB.     

机械活化改性果胶骨架片的制备及释放特性研究

以果胶为原料,采用机械活化法改性,研究了机械活化时间对果胶水溶性和溶胀性的影响,制备了骨架片,探讨了粘合剂、钙盐种类、机械活化时间、载药量和压片压力对骨架片制备的影响,通过BSA含量的测定,研究了机械活化骨架片的释放特性。机械活化改性,降低了果胶的水溶性和溶胀度;骨架片的最佳工艺,0.025g MA 8h,0.008g BSA,0.025g甲基纤维素,0.008g CaSO4与0.001g硬脂酸镁,压片压力8kg·mm-2。机械活化改性果胶骨架片具有更高的化学活性,能使骨架片外表层迅速形成致密凝胶层,与水溶性小的CaSO4形成果胶钙沉淀,有效地减缓水分在骨架片中的扩散。药物在凝胶层膜内溶解并饱和,通过自由扩散作用向膜外扩散。而薄的凝胶层中浓度梯度大,药物快速释放到介质中,表现为药物的初始释放度大。机械活化改性果胶致密而薄的凝胶层和果胶钙沉淀的egg-box空间网状结构大大降低了溶剂的扩散作用,药物释放速度减慢并最终趋于稳态,表现为骨架片释药速度的恒定。     

Effect of Surface Free Energy of Film Laminated Steel Sheets on Content Release Properties

Polyethylene terephthalate (PET) sheets that are now widely used in beverage cans have excellent properties of formability, corrosion resistance and adhesion to steel sheets. To expand their application, we have sought to develop a new PET film laminated steel sheet for use in food cans. Content release properties are necessary for easy removal of the can contents in food can applications. However, PET film laminated steel sheets have poor content release properties. Investigations of these properties have revealed dependence on the strength of adhesion between the films and can contents. The surface free energy of PET films has been inferred to be the main factor in poor content release properties. Therefore, using films with widely diverse surface free energy values, we studied the effects of surface free energy on the content release properties of materials in contact with cans. The results showed that these properties are closely related to the surface free energy of the film material, and that materials with surface free energy of less than 23 mN/m or greater than 44 mN/m show excellent properties for processed meat products with high protein content. The material with PET film coated with mixture of polyester resin and fatty acid is the most promising material for use in food cans in this study. The work has also shown that content release properties can be expressed as a function of adhesion in water between a material and protein. Reducing adhesion can significantly improve content release properties.     

Influence of Hydroxypropyl Methylcellulose Mixture,Apparent Viscosity,and Tablet Hardness on Drug Release Using a 23 Full Factorial Design

ABSTRACT

This study investigates the effects of three factors: (1) use of a mixture of two different grades of hydroxypropyl methylcellulose (HPMC), (2) apparent viscosity, and (3) tablet hardness on drug release profiles of extended-release matrix tablets. The lot-to-lot apparent viscosity difference of HPMC K15M on in vitro dissolution was also investigated. Four test formulations were made, each containing 10% of a very water-soluble active pharmaceutical ingredient (API), 32% HPMC K15M, or a mixture of HPMC K100LV and HPMC K100M, 56% diluents, and 2% lubricants. Each formulation was made at two hardness levels. A 2³ full factorial design was used to study various combinations of the three factors using eight experiments conducted in a randomized order. Dissolution studies were performed in USP apparatus I. The values of t_50% (time in which 50% drug is released) and t_lag (lag time, the time taken by the matrix tablet edges to get hydrated and achieve a state of quasi-equilibrium before erosion and the advance of solvent front through the matrix occur) were calculated from each dissolution profile. The similarity factor (f₂) was also calculated for each dissolution profile against the target dissolution profile. A simple Higuchi-type equation was used to analyze the drug release profiles. Statistical analysis using analysis of variance (ANOVA) and similarity factor (f₂) values calculated from the data indicated no significant difference among the t_50% values and dissolution profiles respectively for all formulations. Within the 3.3–6 kp hardness range investigated, dissolution rates were found to be independent of tablet hardness for all the formulations. Although significantly shorter lag times were observed for the tablets formulated with low- and high-viscosity HPMC mixtures in comparison to those containing a single grade of HPMC, this change had no significant impact on the overall dissolution profiles indicated by the similarity factor f₂ values. From this study it can be concluded that lot-to-lot variability in apparent viscosity of HPMC should not be a concern in achieving similar dissolution profiles. Also, results indicated that within the viscosity range studied (12,000–19,500 cps) an HPMC mixture of two viscosity grades can be substituted for another HPMC grade if the apparent viscosity is comparable. Also, the drug release is diffusion-controlled and depends mostly on the viscosity of the gel layer formed.     

Tableting of Eudragit RS and Propranolol Hydrochloride Solid Dispersion: Effect of Particle Size,Compaction Force,and Plasticizer Addition on Drug Release

The application of a solid dispersion (SD) system of propranolol HCl and Eudragit RS was evaluated in the preparation of prolonged release tablets. The effects of SD size fraction, compaction force, and inclusion of plasticizers [namely diethylphtalate (DEP) and triethylcitrate (TEC)] on crushing strengths of matrices and release profile of drug were also investigated. The results showed that when compressed as a tablet, the SD system was more efficient in prolonging drug release than physical mixture. This effect was due to formation of much harder tablets of the SD system (crushing strength 8.5 kg) compared with those of physical mixtures (crushing strength 2.7 kg). All matrices of the SD system showed release rate patterns that were best described by the Higuchi equation. It was also shown that the rate of drug release decreased from 19.8% to 9.13% min^??1/2 as the SD size fraction decreased from 300–350 to 125–250 µm. However, further reduction of size fraction did not significantly affect tablet crushing strength and drug release rate. Increase in compaction force from 5 to 30 kN increased the crushing strength of matrices from 2.9 to 13.6 kg. However, the rate of drug release remained nearly unchanged beyond compaction pressure of 10 kN, indicating that crushing strength of matrices in the range of 8.5–13.6 kg did not affect drug release rate. The addition of 5% or 10% of either plasticizer (DEP or TEC) led to an increase in crushing strength of matrices and more retardation of drug release. This effect was more pronounced for higher concentrations of plasticizers. This effect was probably due to more plastic deformation of matrices under the compaction force, which helped matrices to retain their shape throughout the dissolution test.