Influence of methacrylic acid and hydroxypropylmethyl cellulose on the tablet properties and in vitro release of dextromethorphan hydrobromide

The release of dextromethorphan hydrobromide from matrices containing hydroxypropylmethyl cellulose (HPMC K100LV) and methacrylic acid copolymer (Eudragit L100-55) has been evaluated at different ratios of the polymers. The physicochemical properties (including weight, thickness, crushing strengh, friability and disintegration time) were also determined at 1000, 2000 and 4000 p compression forces. No significant differences in weight uniformity and thickness values were observed between the different formulations. The crushing strength of the tablets increased with increasing compression force and it reached a constant level at 4000 p. The formulations containing only HPMC K100LV resulted in an extended release pattern, however, Eudragit L100-55 alone could not effectively prolong the drug release. A combination of HPMC K100LV and Eudragit L100-55 in a 1:1 ratio at the 40% level provided an almost similar drug release profile than the marketed product.     

Effect of Kollidon? SR on the release of Albuterol Sulphate from matrix tablets

The objective of this study was to evaluate Kollidon SR for the development of extended release Albuterol Sulphate matrix tablets in comparison with other polymers as Hydroxypropylmethylcellulose K15M, Carbopol 71G NF, and Eudragit L100-55. The mechanical properties of the tablets were improved as concentration of Kollidon SR or other polymers increased. It was found that Kollidon SR 30% (w/w) and HPMC 30% (w/w) tablets have f₂ similarity factor of 83.5 in their Albuterol Sulphate dissolution profile. The marketed product was found to release 99.7% of drug content within 8 h, while Kollidon SR and HPMC tablets with 30% (w/w) polymer concentration level released 92.7% and 92.9% respectively of drug content within 8 h. Kollidon SR has a unique character of maintaining tablets geometric shape until the end of dissolution test, this is mainly due to the water insoluble content, polyvinyl acetate, forming 80% (w/w) of Kollidon SR, while the remaining content 20% (w/w) is the water soluble, polyvinylpyrrolidone, responsible for pore formation causing a diffusion controlled release. Drug release from all previous formulations is best described to be controlled by more than one kinetic mechanism of release.In conclusion, Kollidon SR and HPMC and Carbopol were found to be potential candidates for the development of extended release of Albuterol Sulphate tablets.     

Preparation of multiple-unit floating-bioadhesive cooperative minitablets for improving the oral bioavailability of famotidine in rats

Abstract

The aims of this study were to prepare fine famotidine-containing floating-bioadhesive cooperative minitablets and to investigate the possibility of using those minitablets as a delivery system for promoting the oral bioavailability of famotidine. Nine minitablet formulations were designed using hydroxypropylmethylcellulose (HPMC K4M) as release-retarding polymers, Carbopol 971P as bioadhesive materials and sodium bicarbonate (NaHCO₃) as gas formers. The prepared 3?±?0.02?mm minitablets were evaluated in terms of their swelling ability, floating behavior, bioadhesion test and in vitro release. The optimized minitablets (F6) containing HPMC K4M (50.00%, w/w), Carbopol 971P (10.00%, w/w) and NaHCO₃ (10.00%, w/w) were found to float in 1?min and remain lastingly buoyant over a period of 8?h in vitro, with excellent bioadhesive properties (20.81?g) and sustained drug release characteristics (T_50%?=?46.54%) followed one-order model. In addition, plasma concentration–time profiles from pharmacokinetic studies in rats dosed with minitablets showed 1.62-fold (p?<?0.05) increased absorption of famotidine, compared to the market tablets XinFaDing®. These studies demonstrated that the multiple-unit floating-bioadhesive cooperative minitablets may be a promising gastro-retentive delivery system for drugs that play a therapeutic role in the stomach.     

Development and characterization of Eudragit based mucoadhesive buccal patches of salbutamol sulfate

For systemic drug delivery, the buccal region offers an attractive route of drug administration. Salbutamol sulfate is a short-acting β₂-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It’s oral bioavailability is ∼40% due to extensive first pass metabolism. Salbutamol sulfate patches were prepared using Eudragit L-100, HPMC, PVA and Carbopol 934 in various proportions and combinations using PEG-400/PG as plasticizers. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches were ranged between 0.23 ± 0.008 and 0.59 ± 0.007 mm and mass varied between 65.23 ± 3.3 and 117.92 ± 4.2 mg. Patches showed an increase in mass and swelling index with PEG-400 when compared with PG. The surface-pH of patches ranged between 6 and 7. Formulations E7 (7.5 mL Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PEG-400), E12 (7.5 mL Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PEG-400), F7 (7.5 mL Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PG), and F12 (7.5 mL Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PG) showed high folding endurance. Residence time of the tested patches ranged between 101 and 110 min. The maximum in vitro release was found to be 99.93% over a period of 120 min for formulation F12. Data of in vitro release from patches were fitted to different kinetic models such as Higuchi and Korsmeyer–Peppas models to explain the release profile. Formulations E7 and F7 were best fitted to the non-Fickian, where as formulations E12 and F12 showed Fickian/anomalous drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period.     

盐酸帕罗西汀肠溶缓释片的制备及体外释放研究

目的制备盐酸帕罗西汀肠溶缓释片,并对其体外释放度进行考察。方法采用HPMC K100LV和HPMC K4M作为骨架材料,以水乳糖为填充剂制备盐酸帕罗西汀缓释片芯,再使用Eudragit L30D-55包肠溶衣,制成盐酸帕罗西汀肠溶缓释片,并采用f_2相似因子法评价自制制剂和参比制剂在释放介质中的体外释放行为。结果体外释放度实验显示,自制制剂和参比制剂的f_2相似因子值大于50。结论制备的盐酸帕罗西汀肠溶缓释片的释药行为与参比制剂的体外释放行为相似。     

In vitro Evaluation of the Effect of Combination of Hydrophilic and Hydrophobic Polymers on Controlled Release Zidovudine Matrix Tablets

The aim of the present study was to prepare and characterize controlled-release matrix tablets of zidovudine using hydrophilic HPMC K4 M or Carbopol 934 alone or in combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using USP XXIV dissolution apparatus No.2 (paddle) type. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix tablet surface. The in vitro results of controlled – release zidovudine tablets were compared with conventional marketed tablet Zidovir. The in vitro drug release study revealed that HPMC K4 M or Carbopol 934 preparation was able to sustain the drug release near to 6 hours. Combining HPMC K4 M or Carbopol 934 with ethyl cellulose sustained the drug release for nearly 12 h. The in vitro evaluation showed that the drug release may be by diffusion along with erosion. Results suggest that the developed controlled-release tablets of zidovudine could perform therapeutically better than marketed dosage forms, leading to improve efficacy, controlling the release and better patient compliance.     

Effect of anionic polymers on the release of propranolol hydrochloride from matrix tablets.

Anionic polymers, namely Eudragit S, Eudragit L 100-55, and sodium carboxymethylcellulose, were incorporated into hydroxypropylmethylcellulose (HPMC K100M) to modify the drug release from HPMC matrices. The effects of changing the ratio of HPMC to anionic polymers were examined in water and in media with different pH. The dissolution profiles were compared according to release rates. The interaction between propranolol hydrochloride and anionic polymers was confirmed using the UV difference spectra method. The drug release was controlled with the type of anionic polymer and the interaction between propranolol hydrochloride and anionic polymers. The HPMC-anionic polymer ratio also influenced the drug release. The matrix containing HPMC-Eudragit L 100-55 (1:1 ratio) produced pH-independent extended-release tablets in water, 0.1 N HCl, and pH 6.8 phosphate buffer.     

Formulation,Characterization, and In Vitro Evaluation of Bioadhesive Gels Containing 5-Fluorouracil

The objective of this study was to prepare and evaluate in vitro the bioadhesive gels of 5-Fluorouracil (FU) for the treatment of oropharyngeal cancer. In preformulation study, the physicochemical interactions between FU and polymers were investigated by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, and differential scanning calorimetry (DSC). According to FTIR, XRD, and DSC studies, the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. The gel formulations containing FU were prepared by using Poloxamer 407, HPMC K 15 M, and Gantrez® S-97 (polymethylvinylether-co-maleic anhydride). The formulations contained Poloxamer 407 (16–18% w/w) either alone or in combination with HPMC K 15 M and Gantrez® S-97. The bioadhesiveness of the gels was found to increase with increasing proportion of HPMC K 15 M and Gantrez® S-97. In vitro release studies indicated that release could be sustained up to 8 hr. The permeability coefficients (Kp) of gel across cellulose membrane and buccal mucosal membrane were 1.06 × 10^?4 cm/s and 3.94 × 10^?5 cm/s, respectively, and differed significantly (p < 0.05). Increasing temperature increased the drug release by increasing drug diffusion despite increase in viscosity. The pH of the release medium showed a very slight effect on the release of FU. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as non-Fickian diffusion.     

Preformulation-Assisted Design and Characterization of Modified Release Gastroretentive Floating Extrudates Towards Improved Bioavailability and Minimized Side Effects of Baclofen

Baclofen immediate release mode of administration exhibit sharp plasma peaking that results in the emergence of side effects like hypotension. This research employs preformulation studies to design an optimum dosage form for baclofen to enhance therapeutic outcomes. These studies include partition coefficient and ex-vivo permeation studies. Partition coefficient was found to be 1.27 at pH 7.4. Permeation studies confirmed the presence of specialized transport mechanism through the GIT. It was concluded that an ideal formulation of baclofen should provide slow-release of the drug to avoid sharp peaking. Modified-release floating extrudates of baclofen were prepared using Carbopol 934 and HPMC with different gas-forming agents. Different release-retarding materials (Eudragit L100, Eudragit RS100 and Cetyl alcohol) were used as ingredients in the binder solutions. The prepared extrudates were assessed for their drug content, floating ability, friability properties and in vitro release properties. The prepared extrudates recorded buoyance characteristics for 24 h with a floating lag time varying from 0 to 73.34 s. The optimized extrudates manifested extended baclofen release for up to 8 h compared to 0.2 h for marketed baclofen tablets. This approach was found efficient to provide greater bioavailability and minimize hypotension associated with commercial baclofen tablets.     

Improved drug delivery to the lower intestinal tract with tablets compression-coated with enteric/nonenteric polymer powder blends

The objective of this study was to develop pH-erosion-controlled compression-coated tablets for potential colonic drug delivery with improved gastric resistance and pulsatile release based on compression-coatings of powder blends of the enteric polymer Eudragit® L100-55 and the extended release polymer ethylcellulose. Tablet cores containing model drugs of varying solubilities (acetaminophen, carbamazepine and chlorpheniramine maleate) were compression-coated with different ratios of Eudragit® L100-55:ethylcellulose 10cP FP at different compression forces and tablet core:compression-coat ratios. The compression-coated tablets were characterized by drug release, media uptake, erosion behaviour and wettability. All drugs were released in a pulsatile fashion in higher pH-media after a lag time, which was controlled by the erosion properties of the Eudragit L:ethylcellulose compression-coating. The addition of ethylcellulose avoided premature drug release in lower pH-media and significantly increased the lag time in higher pH-media because of a reduction in wettability, media uptake and erosion of the compression-coatings. Importantly, ethylcellulose also reduced the pH-dependency of the erosion process between pH 5.5 and 7.4. The lag time could also be increased by increasing the compression force and decreasing the core:compression-coat ratio. In conclusion, tablets compression-coated with blends of Eudragit L and ethylcellulose resulted in excellent release properties for potential targeting to the lower intestinal tract with no release in lower pH-media and rapid release after a controllable lag time in higher pH-media.     

Formulation development of Carvedilol compression coated tablet

Purpose: The aim of present research was to produce carvedilol compression coated tablet to provide biphasic drug release.

Method: A compressed coated tablet made of a sustained release core tablet and an immediate release coat tablet. Both the core and the coat contained carvedilol. The sustained release effect was achieved with polymers (HPMC K₄M and PEO WSR 205) to modulate the release of the drug. The powder blends for core and coat tablets were evaluated for angle of repose, bulk density, compressibility index, and drug content. Compressed coated tablets were evaluated for thickness, diameter, weight variation test, drug content, hardness, friability, disintegration and in vitro release studies.

Result: The powder blends showed satisfactory flow properties, compressibility, drug content and all the tablet formulations showed acceptable pharmaco-technical properties. Carvedilol contained in the fast releasing component was released within 3?min, whereas the drug in the core tablet was released at different times up to 24?h, depending on the composition of the matrix tablet. The mechanism of drug release was fickian diffusion or anomalous behavior.

Discussion: Batch F7, containing 10?mg PEO WSR 205 and 5?mg HPMC K₄M, showed maximum similarity with theoretical profile and zero order drug release kinetic.     

乙酰螺旋霉素口腔贴片的研制及体外释药的考察

目的:研制乙酰螺旋霉素口腔贴片。方法:以卡波姆934P和HPMC(K4M)作为黏附材料,制备口腔贴片,并对其生物黏附力及体外释放度进行了考察,采用一阶导数光谱法测定乙酰螺旋霉素的含量。结果:卡波姆934P的生物黏附性优于HPMC,体外释放均符合Higuchi方程,HPMC的缓释效果优于卡波姆934P。结论:处方中以卡波姆934P与HPMC配比为1:1时为最优处方。     

阿昔洛韦胃漂浮缓释片的制备及体外释放

目的制备阿昔洛韦胃漂浮缓释片,并通过紫外分光光度法考察其体外释放影响因素。方法以阿昔洛韦为模型药物,分别以壳聚糖、羟丙基甲基纤维素K15M(HPMC K15M)、Eudragit S100和碳酸钙为基质制备胃漂浮缓释片,用释放度测定法考察影响药物释放的因素。结果随着HPMC K15M用量增加,药物的释放显著减慢,碳酸钙用量增加,药物释放加快。结论制备的阿昔洛韦胃漂浮缓释片漂浮性良好,且能够达到缓释的目的。     

盐酸文拉法辛缓释片的初步研究

目的：制备盐酸文拉法辛缓释片并考察其体外释放特性。方法：利用正交设计优化处方，建立释放度测定方法，根据不同时间累积释放度考察药物的释放情况，并采用不同方程拟合释放曲线。结果：用55％ HPMC K100M制得缓释片，其释放曲线可用一级方程动力学拟合。结论：用55％ HPMC K100M制备的盐酸文拉法辛缓释片具有良好的释药效果。     

Fast and pH-dependent release of domperidone from orally disintegrating tablets

There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug–polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10?min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation.     

Development and in vitro evaluation of buccoadhesive carvedilol tablets

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2)) permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane. BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.     

Comparative pharmaceutical study on colon targeted micro-particles of celecoxib: in-vitro–in-vivo evaluation

In order to target celecoxib which is a COX2 inhibitor, with potentials in the prevention and treatment of colitis and colon cancer, it was formulated as microparticles using the solvent/evaporation method and various pH-dependent Eudragit polymers. The in-vitro evaluation of the prepared microparticles showed spherical and smooth morphology. The encapsulation efficiency and yield were high, indicating that the method used is simple and efficient at this scale. The in-vitro release study showed no release in the acidic medium for 2?h followed by the release of the drug in pH 6.8 in case of Eudragit L100-55 and L100 and pH 7.4 in case of Eudragit S100. The pharmacokinetic parameters were calculated and method validation was performed to insure that it is suitable and reliable. Pharmacokinetic parameters were investigated by determining the C_max, T_max, AUC_0–t, K_el, and t_1/2 of the drug as a suspension and as microparticles. There was a significant difference (p?<?0.05) in T_max between the drug as a suspension and as microparticles. The effect of celecoxib on the degree of inflammation was examined on acetic acid induced colitis rat model and the drug was given as a suspension and as microparticles. The evaluation was done using macroscopical, microscopical and biochemical examination. There was a significant difference between the acetic acid control group and the treatment groups regarding all examination criteria in the order microparticles formulated using Eudragit S100 followed by Eudragit L100-55 while microparticles using Eudragit L100 and drug suspension showed almost the same results.     

Influence of methacrylic and acrylic acid polymers on the release performance of weakly basic drugs from sustained release hydrophilic matrices

Weakly basic drugs and their salts exhibit a drop in aqueous solubility at high pH conditions, which can result in low and incomplete release of these drugs from sustained release formulations. The objective of this study is to modulate matrix microenvironmental pH by incorporation of acidic polymers and thus enhance the local solubility and release of basic drugs in high pH environment. Two weakly basic drugs, papaverine hydrochloride and verapamil hydrochloride with widely different pKa and aqueous solubilities at the pH of interest (6.8), were investigated for their release from hydrophilic matrices and the effect of a methacrylic (Eudragit L100-55) and an acrylic acid polymer (Carbopol 71G), were studied. For papaverine HCl, release increased with an increase in the levels of the acidic polymer used. Direct measurement of matrix pH using microelectrodes illustrated that the mechanism of release enhancement was based on modulation of microenvironmental pH. For verapamil HCl, incorporation of L100-55 resulted in release retardation due to an interaction between the anionic polymer and the cationic drug and the extent of retardation increased with an increase in the polymer level. The interaction product was characterized by NIR, FT-IR, and MTDSC techniques. Verapamil HCl release from Carbopol 71G based matrix tablets was higher than that from conventional hydroxypropyl methylcellulose (HPMC) based matrices, without any incorporated acidic additives.     

Influence of HPMC K100LV and Compritol® HD5 ATO on Drug Release and Rheological Behavior of HPMC K4M Matrix Tablets

Purpose

The objectives of this study were to develop once-a-day oral controlled-release tablets of quetiapine fumarate (QF) and to determine the effect of polymer type, viscosity grade, polymer ratio, and polymer rheological properties on the rate of QF release from hydroxypropyl methylcellulose (HPMC) matrix tablets.

Methods

Tablets were prepared from low-viscosity-grade HPMC K100LV (K100LV), high-viscosity-grade HPMC K4M (K4M), Compritol® HD5 ATO (PEGylated glyceryl behenate (PGB)), and binary combinations of these polymers. In vitro drug release from all tablets was evaluated over 24 h.

Results

In vitro drug release studies revealed that formulations containing K100LV/K4M and PGB/K4M at a ratio of 170:70 resulted in similar release profiles which extended for 24 h (f2 > 50). QF release kinetics followed either diffusion, anomalous transport, case II transport, or super case II transport, as fitted by the Korsmeyer-Peppas model. Tablet swelling and erosion studies were consistent with dissolution profiles. A linear relationship between % swelling and % QF released was observed in tablets containing K4M alone or in combination with K100LV or PGB, indicating the direct role of polymer swelling in controlling the mechanism of drug release. The viscoelastic properties of single and binary polymeric gels made with the three polymers (K100LV, K4M, and PGB) corroborated the in vitro release studies of QF tablets.

Conclusions

Our results provide evidence that blending polymers with different viscosities and hydrophilicities can result in unique matrices with tunable release profiles.

     

Investigating effects of hydroxypropyl methylcellulose (HPMC) molecular weight grades on lag time of press-coated ethylcellulose tablets

The research undertaken exemplifies the effects of hydroxypropyl methylcellulose (HPMC) molecular weight (MW) grades of on lag time of press-coated ethylcellulose (EC) tablets. The formulation comprised an immediate release core (containing prednisone as a model drug) surrounded by compression coating with variegated EC-HPMC blends. Five selected HPMC grades (E5, E15, E50, K100LV and K4M) were explored at three different concentrations (10% w/w, 20% w/w and 30% w/w in outer coat) to understand their effects on lag time and drug release. In vitro drug release testing demonstrated that, with increase in concentration of E5 and E15, up to 30% w/w, the mean lag time decreased progressively; whereas with remaining grades, the mean lag time initially decreased up to 20% w/w level and thereafter increased for 30% w/w level. Importantly, with increase in HPMC concentration in the outer coat, the variability in lag time (%RSD; n?=?6) was decreased for each of E5, E15 and E50, whereas increased for K100LV and K4M. In general, the variability in lag time was increased with increase in HPMC MW at studied concentration levels. Markedly, tablets with 30% w/w K4M in outer coat exhibited slight premature release (before the rupture of outer coat) along with high variability in lag time. Overall, the study concluded that low MW HPMCs (E5, E15 and E50) were found rather efficient than higher MW HPMCs for developing robust EC-based press-coated pulsatile release formulations where precise lag time followed by sharp burst release is desired.