ArticleLiterature Review

Carbomers and their use in pharmaceutical technology

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Carbomers, high-molecular polymers based on acrylic acid, are employed in the technology of drugs as auxiliary substances acting as emulsifiers, gel-forming substances, stabilizers of suspensions, and binders in tablets. Their properties are utilized to control release as well as to improve biological availability of drugs. They are physiologically inert, non-sensitizing, and possess excellent thermal stability. They are used for various routes of administration: topical, oral and peroral, vaginal and rectal.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... When dispersed in water, carbomer disperse quite well and forms viscous suspension at pH 2.8-3.2 [6]. Meanwhile, the mechanism of gel formation using carbomers is based on neutralization, leading to acids conversion to the corresponding salts, therefore, alkali addition is necessary [7,8]. ...
... Meanwhile, the mechanism of gel formation using carbomers is based on neutralization, leading to acids conversion to the corresponding salts, therefore, alkali addition is necessary [7,8]. The carbomer gel can be sterilized by several methods including gamma radiation [6]. ...
Article
Full-text available
Objective: This study aims to prepare sterile gel containing aloe vera (AV) powder and evaluate its physicochemical properties after sterilization by gamma radiation. Methods: The gel was prepared using carbomer as stabilizer, and sterilized by gamma radiation. The physical stability was evaluated including organoleptic, pH, viscosity and sterilization. Furthermore, malic acid concentration was determined as a marker compound contained in the gel. Results: The gel was successfully prepared containing 20% AV powder and 25% carbomer. The physical properties including organoleptic, pH and viscosity were not significantly changed after sterilization, and also stable even after 28 storage days. Meanwhile, malic acid concentration before and after sterilization were 47.2 mg/ml and 43.9 mg/ml, respectively. This showed the physicochemical properties were not significantly different after sterilization. Conclusion: Gamma radiation is suitable to sterilize gel containing AV powder.
... Carbomers allow to obtain highly-viscous gels of good quality even at low concentrations of a substance-former. They are known for their excellent bioadhesive, thermostable, and organoleptic properties, and therefore, these gelling agents are attractive from both the pharmaceutical and consumer point of view [19][20][21]. In addition, carbomers are compatible with many active ingredients and allow to achieve the required pH value [22,23]. ...
Article
Full-text available
The physicochemical properties, especially pH value of dental medicines, have significant influence on the health of oral cavity tissues. The pH of formulations should correspond to the value of saliva pH (5.5–8.0). For carbomer-based gels, the required pH value is obtained by neutralizing them with alkaline components, which leads to their structuring (thickening). This affects the physical properties of the gel, its residence time at the application site and the rate of release of active pharmaceutical ingredient. Therefore, the main purpose of this study is to evaluate the rheological, textural, and biopharmaceutical properties of Carbomer Polacril® 40P-based dental gel depending on the pH value. Evaluation of the rheological properties of gel preparations were performed by measuring the structural viscosity of the samples as a function of pH and temperature. The textural properties of the gel were evaluated by performing tests regarding back extrusion and spreadability. Carbomer Polacril® 40P-based gels haven’t shown noticeable thixotropic behavior, and were characterized by plastic flow in the whole studied pH range. The structural viscosity at the selected average pH value hasn’t differed at storage (25 °C) and application (37 °C) temperature. Texture studies of dental gels have shown a strong correlation with rheoparameters. Their rheological behavior and textural properties haven’t changed significantly between the pH range of 5.5–6.6. The relatively narrow range of working pH values does not affect the change in the viscosity of the preparation significantly and, consequently, does not affect the release of APIs from the developed Carbomer Polacril® 40P-based dental gel.
... Carbopols, hydrophilic polyanionic carbomers, are polymers of acrylic acid cross-linked with polyalkenyl ethers or divinyl glycol. Carbopols have found use in a diverse range of pharmaceutical applications ranging from controlled release solid dosage formulations to bioadhesive and topical applications [33, 34]. Particularly in vaccines, Carbopol-based adjuvant suspensions have been evaluated in veterinary vaccines since the 1970's against several pathogens, including equine influenza virus [35], porcine parvovirus [36], Staphylococcus aureus mastitis (in sheep) [37], etc. ...
Article
Identification of optimal antigen(s) and adjuvant combination(s) to elicit potent, protective, and long-lasting immunity has been a major challenge for the development of effective vaccines against chronic viral pathogens, such as HIV-1, for which there are not yet any licensed vaccines. Here we describe the use of a novel adjuvant approach employing Carbopol 971P(®) NF (hereafter referred to as Carbopol971P), a cross-linked polyanionic carbomer, in combination with the Novartis proprietary oil-in-water adjuvant, MF59, as a potentially safe and effective adjuvant to augment humoral immune responses to the HIV-1 envelope glycoprotein (Env). Intramuscular immunization of small animals with recombinant Env glycoprotein (gp140) formulated in Carbopol971P plus MF59 gave significantly higher titers of binding and virus neutralizing antibodies as compared to immunization using gp140 with either MF59 or Carbopol971P alone. In addition, the antibodies generated were of higher avidity. Importantly, the use of Carbopol971P plus MF59 did not cause any serious adverse reactions or any obvious health problems in animals upon intramuscular administration. Hence, the Carbopol971P plus MF59 adjuvant formulation may provide a benefit for future vaccine applications.
Article
The main limitation to the success of central nervous system (CNS) therapies lies in the difficulty for drugs to cross the blood-brain barrier (BBB) and reach the brain. Regarding its structure and enzymatic complexity, crossing the BBB is a challenge, although several alternatives have been identified. For instance, the use of drugs encapsulated in lipid nanoparticles has been described as one of the most efficient approaches to bypass the BBB, as they allow the passage of drugs through this barrier, improving brain bioavailability. In particular, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been a focus of research related to drug delivery to the brain. These systems provide protection of lipophilic drugs, improved delivery and bioavailability, having a major impact on treatments outcomes. In addition, the use of lipid nanoparticles administered via routes that transport drugs directly into the brain seems a promising solution to avoid the difficulties in crossing the BBB. For instance, the nose-to-brain route has gained considerable interest, as it has shown efficacy in 3D human nasal models and in animal models. This review addresses the state of the art on the use of lipid nanoparticles to modify the pharmacokinetics of drugs employed in the management of neurological disorders. A description of the structural components of the BBB, the role of the neurovascular unit and limitations for drugs to entry into the CNS is first addressed, along with the developments to increase drug delivery to the brain, with a special focus on lipid nanoparticles. In addition, the obstacle of BBB complexity in the creation of new effective drugs for the treatment of the most prevalent neurological disorders is also addressed. Finally, the proposed strategies for lipid nanoparticles to reach the CNS, crossing or circumventing the BBB, are described. Although promising results have been reported, especially with the nose-to-brain route, they are still ongoing to assess its real efficacy in vivo in the management of neurological disorders.
Chapter
A primary concern in treating pediatrics with formulations is the lack of standard specifications for marketing the products for children. The shortage of pediatric medicines motivates health professionals to use marketed adult formulations in an off-labeled way. As many reports revealed, excipients used in off-labeled formulations in pediatric populations pose severe harmful effects. Hence, the thorough investigation of the toxic nature of the excipients used in the formulations for treating pediatric patients must be evaluated with utmost care to avoid toxic reactions in children. On the other side, guidelines provided by various regulatory agencies on drugs and excipients should be followed to meet the acceptable criteria for the safety and quality of pharmaceutical drug products. In addition, any novel excipient used in formulation development should have comprehensive safety and toxicity profile data. So that interaction assessment is easy to understand, which further helps determine the adverse drug event in the formulation.
Conference Paper
Red, brown and Green algae contain antioxidant and have the potential as anti-aging but still rarely developed for cosmetic ingredients. The purpose of this study was to investigate the chemical constituent, total phenol and flavonoid content, antioxidant activity and toxicity of algae extract and formulated into serum preparation. Padina Australis, Ulva Reticulata, Sargassum Oligocystum, dan Euchema Cottonii contain chemical constituent hexadecanoic acid, methyl ester, fatty acid and phytol which possess antioxidant activity. P. australis has the highest total phenol and flavonoid content that is 106 mgGAE/100 gr and 30.516 mgQE/g respectively. Antioxidant activity of P. australis, U. reticulata, E. cottoni and S. oligocystum is stated in IC50 value which are 2693.33, 2679.16, 4407.57 and 1700 µg/ml respectively wherein it still considered as low antioxidant activity. Algae extract in this study also proven to have low toxicity with LC50 higher than 1000 ppm. Algae crude extract was formulated into anti-aging serum formulation and evaluated for one month by accelerated stability test method. This stability test observed physical properties pH, viscosity, refractive index, and specific gravity and chemical properties. Based on the stability test results on each anti-aging serum formulas, formula with E. cottoni extract showed the stable formulation for serum preparation with no significant chemical and physical change due to temperature alteration during accelerated stability test.
Article
Background At the same dosage, the new generation of Sabin IPV (sIPV) is less immunogenic than the traditional oral polio vaccine (OPV) dosage in China [1]. The useful adjuvant might be necessary strategy to strengthen the immune protective effects; Methods In this study, we produced an adjuvant compound (named KML05) that could promote immunogenicity and fractional doses of Sabin‐inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model. The compound adjuvant had both advantages and a function of MF59 and carbopol971P. Results The effect seroconversion of experimental animals immunized with KML05 could be extended to one‐eighth of the dose. According to the result of the geometric mean titters (GMTs), KML05 adjuvant could save eight times the amount of sIPV D‐antigen usage, but aluminum hydroxide adjuvant could save twice at the same titters. Additionally, it was found that there was a significant difference in the GMT titter of poliovirus type 2 between animals immunized by KML05 and alum adjuvant (P<0.05). At twelfth months post vaccination, the neutralization titters stimulated by IPV‐KML05 were maintained over a longer time period in immunized animals. Conclusion Our research team developed KML05 adjuvant, which combined carbopol971P with MF59, increased antibody responses to sIPV for a longer duration of protection in a rat model. This article is protected by copyright. All rights reserved.
Article
Full-text available
The objective of the present study was to assess safety and efficacy of a new modified live-virus porcine reproductive and respiratory syndrome (PRRS) genotype 1 vaccine in pregnant sows at various stages of gestation under field conditions. A total of 505 sows and gilts were allocated to two treatment groups and maintained in separate facilities. Animals of group 1 were vaccinated with a commercial modified live genotype 1 PRRSV vaccine (control product, CP), while animals of group 2 were immunized with a new modified live genotype 1 PRRSV vaccine (investigational veterinary product, IVP) (ReproCyc® PRRS EU, Boehringer Ingelheim Vetmedica GmbH). Injection site reactions were noted to be significantly less frequent in the IVP group compared to the CP group for pain (p = 0.039), redness (p = 0.030), heat (p = 0.016) and swelling (p = 0.002). The mean total number of piglets alive at weaning did not differ significantly between both study groups (10.6 vs. 11.0, p = 0.375). However, pre-weaning mortality was significantly higher (p = 0.005) in piglets from the CP group (14.1% vs. 10.9%). Analyses of reproductive performance data for both groups did not result in statistically significant differences between CP group and IVP group for number of piglets alive (12.7 and 12.6, respectively), healthy live (11.9 and 11.8), weak (0.7 and 0.5), stillborn (1.0 and 0.8) and mummified piglets (0.3 and 0.2) per litter. No differences were detected between both groups for piglet birth weights, while body weights at weaning (7.2 kg vs. 6.6 kg, p = 0.026) and average daily gain (0.2445 kg vs. 0.2211 kg, p = 0.037) were significantly higher in piglets from the IVP group. In conclusion, the administration of a single dose of ReproCyc® PRRS EU to sows and gilts at various stages of gestation confirmed non-inferiority to a commercial PRRS vaccine regarding safety and efficacy parameters under field conditions.
Article
Full-text available
Swellable-matrix tablets based on hydrophilic polymers are simple dosage forms with controlled release, which are currently used in pharmacotherapy of many diseases. The most commonly used polymer is (hydroxypropyl)methylcellulose (hypromelose). The drug release from these systems through a gel layer can be modified using additives changing the drug dissolution profile. These excipients can be divided into several groups such as indifferent fillers (soluble or insoluble), substances increasing drug solubility (P-cyclodextrins), excipients forming interactive products (polymers, ion-exchange resins, surfactants) and substances influencing pH in matrix microenvironment (acid and basic modifiers).
Article
BACKGROUND: Recently, the biodegradable materials with good biocompatibility and with no adverse reaction have been widely applied in the clinical treatment and care of gynecology and obstetrics. The development of the biodegradable material is very rapid. OBJECTIVE: To summarize the application of biodegradable materials in gynecology and obstetrics. METHODS: The first author searched PubMed and CNKI databases for articles related to biodegradable materials in gynecology and obstetrics using the keywords of “degraded materials, biodegradable materials, gynecological care, surgery” in Chinese and English respectively. This article has an outlook of the potential application in gynecology and obstetrics based on clinical experience. RESULTS AND CONCLUSION: Biodegradable materials with good biocompatibility and biological security play an important role in biomedical materials. Their polymers and degradation products show small adverse reactions to the body, and have good biomechanical properties, physical and chemical properties and good workability, which have been widely used in gynecology and obstetrics, such as absorbable stylolite and tampon tape. Although we have made a great progress on the biomaterial research, it still has the limitation and safety flaws in the clinic. As the biomaterial research is further developed, the biomaterial application prospect will be more promising. © 2014, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.
Article
Full-text available
This review addresses the general principles of the classification of gel-forming agents, and the characteristics, properties, preparation techniques, and mechanisms of gel formation of the major groups of gel-formers used in producing dosage forms (derivatives of cellulose, carbopols, polyethylene oxides, silicones, poloxamers, alginates, κ -ginanes, bentonite clays, and chitosan), to facilitate selection of polymers for developing dosage forms as gels.
Article
Full-text available
Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that has effects on wounding healing and neuro-protection. However, it is difficult to use bFGF to treat diseases that are separated by physiological barriers, such as the dermal barrier and blood brain barrier. To improve bFGF's penetration ability, we fused the recombinant human fibroblast growth factor (rhbFGF) gene with TAT. We constructed a pET3c vector that contained the recombinant bFGF gene and successfully expressed this gene in the E. coli strain BL21 (DE3) pLsS. The fusion protein was purified using CM Sepharose FF and heparin affinity chromatography. The purity of the TAT-rhbFGF was greater than 95%, as detected by SDS-PAGE. An in vitro MTT trial revealed that the modified bFGF significantly promoted the proliferation of NIH3T3 cells. The cell penetration trial and the mouse skin penetration trial demonstrated that the fusion protein had certain penetration abilities. The animal experiments confirmed that TAT-rhbFGF was effective in the treatment of the hypertrophic scars. We have successfully expressed and purified a TAT-rhbFGF fusion protein in this study. Our results have shown that the fusion protein had a greater ability to penetrate the dermal skin layer. TAT-rhbFGF improved the physical appearance of hypertrophic scars. TAT-rhbFGF may be a potential fusion protein in the treatment of dermal disorders, including hypertrophic scar.
Article
Abstract We previously demonstrated that a commercially available natural product preparation with high content (>90%) of theaflavin derivatives (TFmix) exhibited potent anti-HIV activities. Here we developed a TFmix gel formulation as a topical microbicide candidate. The effect of TFmix on the amyloid fibril formation of semen-derived enhancer of virus infection (SEVI) peptide was detected by transmission electron microscopy. The toxicity of the TFmix gel was evaluated using human vaginal and cervical epithelial cell lines and rabbit vaginal irritation models, respectively. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and immunoregulatory cytokines (IL-10 and GM-CSF) in cervicovaginal lavages (CVLs) were measured by ELISA kits. Proliferating cell nuclear antigen (PCNA) immunostaining was performed to evaluate inflammation in the vaginal tissues. TFmix gel could degrade SEVI-specific amyloid fibrils and showed low cytotoxicity to epithelial cells of the female reproductive tract. No apparent cervicovaginal toxicity was observed at any time point evaluated following the intravaginal administration of TFmix gel to rabbits, whereas application of N-9 gel resulted in damage to the vaginal epithelium. Neither proinflammatory nor immunoregulatory cytokine production was triggered by TFmix gel. Only low expression of PCNA was observed in vaginal tissues of TFmix gel-treated rabbits. The concentration of TFmix in plasma was very low (below the lower limit of quantitation) 1 h after a single vaginal administration of TFmix gel. However, TFmix was still detected in the cervicovaginal lavages (CVLs) 6 h after treatment, indicating that it could be retained in the vaginal cavity for a long period of time. With its potent anti-HIV-1 activity, marked stability at acidic condition, low mucosal toxicity, and lack of systemic absorption, TFmix gel can be considered as an inexpensive and safe microbicide candidate for the prevention of HIV sexual transmission.
Article
The paper focuses on the study of the effect of pH of dissolution medium on the release of diltiazem hydrochloride from carbomeric matrices. Swelling of carbomers, high-molecular cross-linked anionic polymers, is dependent on the value of pH, which decides whether these polymers exist in an ionized or a non-ionized form. In alkaline medium, carboxylic groups of carbomers ionize and hydrate markedly, which also facilitates their interaction with cationic drugs, in this case with diltiazem hydrochloride. The development of a sparingly soluble complex drug-polymer, the presence of which was demonstrated with the use of Fourier IR spectrophotometry, is one of the factors which causes decelerated release of the drug as well as decreased swelling of matrices in this dissolution medium. In both selected dissolution media, an assumption has been confirmed that with an increasing concentration of the polymer in the system a smaller share of the drug is released. Drug release from matrix tablets is also influenced by the rate of dissolution of the drug in dependence on the pH of the medium. Being a salt of a feeble base and a strong acid, diltiazem hydrochloride is more slowly soluble in an alkaline medium than in the medium with pH 1.2. This factor also contributes to its slower release in the medium of phosphate buffer of pH 7.4.
Article
Oral mucoadhesive tablets belong to modern dosage forms, which allow controlled drug release after buccal application. They are used for the treatment of oral cavity disorders or for systemic administration of drugs with high first-pass effect or drugs instable in gastrointestinal tract. This study reports the development of oral mucoadhesive tablets containing antimycotic drug ciclopiroxolamine. Mucoadhesive properties of placebo tablets containing different ratios of carbomer and hydroxypropylmethylcellulose were evaluated in vivo in healthy human volunteers. The longest mucoadhesion for 9 hours was achieved in matrices containing 60% (w/w) of carbomer. When optimum combination of the two mucoadhesive polymers was selected, tablets containing ciclopiroxolamine were prepared and one tablet side was film-coated to make the application procedure easier. Tablet quality parameters were determined and drug dissolution profile was evaluated under different pH conditions. In vitro release of ciclopiroxolamine was slower than the desintegration of prepared mucoadhesive tablets in vivo. Nevertheless, tablets containing 25 mg of ciclopiroxolamine performed prolonged drug release with oral mucosa concentrations higher than its MIC of relevant pathogens.
Article
A drug with cationic characteristics such as procaine can be conveyed in a Carbomer hydrogel in two different ways: (i) in the form of salt in solution in the aqueous phase, and (ii) in the base form salified with the same polymer. Introduction of the drug into the hydrogel with different concentrations of polymer produced, in both cases, a reduction in viscosity in relation to drug concentration. The gels with procaine salified with the polymer showed greater viscosity. The drug release rate, in general, diminished with the increase in polymer concentration. Nevertheless, when this concentration was maintained, there was no variation in release rate when the viscosity produced as a consequence of drug concentration was changed. Gels with procaine salified with the carboxyvinylic polymer had a faster release rate than those with procaine in the hydrochloride form dissolved in the aqueous phase. These results have also been confirmed by a simulated absorption test.
Article
The review paper summarizes the principal pharmaceutical and medical information about the hitherto achieved results in the development of bioadhesive dosage form concentrating on mucoadhesive oral tablets. The site of administration of the tablets is the facial pocket. Due to specific properties of the mucous layer on the buccal mucosa and mucoadhesive polymers from which the tablets are manufactured, tablets adhere to the mucosa. The adhesion may take a certain period of time and during the whole period the active ingredient is gradually released. Absorption of the drug through the mucous membrane of the oral cavity has a number of advantages, in particular with respect to the stability of the drug. Various types of mucoadhesive tablets are being developed. The system releasing the drug only in one direction, i.e. direct to the mucosa, seems to be very advantageous. In the evaluation of mucoadhesive tablets, two parameters are of particular importance, the bioadhesive force and the rate of drug release. Oral mucoadhesive tablets can be employed in the treatment of both systemic and local diseases.
Article
In the present study, investigation of the possibility of interaction of verapamil hydrochloride with Carbopol 934P using differential scanning calorimetric analysis and Fourier transform infrared analysis was performed. The effect of the drug-to-polymer ratio, the electrolyte concentration, and the pH of the medium on the extent of interaction of the drug with the polymer using 2(3) factorial design was investigated. The study also investigated the effect of this interaction on the rate of water uptake of the matrix or the rate of release of verapamil hydrochloride from the swelling polymer matrix. Results revealed that the drug-to-polymer ratio had the most influential effect on both the extent of interaction between the drug and the polymer and the rate of water uptake of the polymer matrix. On the other hand, the pH of the medium had the most significant effect on the rate of drug release. Interaction of the tertiary amine nitrogen of the drug with the anionic carboxyl group on the polymer, forming an insoluble complex, reduced the rate of drug release. This interaction also led to neutralization of the carboxyl group and suppression of the electrostatic repulsion between the anionic groups, which reduced the uncoiling and chain relaxation of the polymer and consequently decreased the swelling of the matrix. The application of the designed experiment allowed the quantification of the effect of each of the studied variables on the investigated responses through the calculation of their coefficient in the response suface equation and checking of their significance.
Article
The objectives of the present study were: (1) to investigate the possibility of using a Carbopol polymeric solution as granulating agent by the fluid bed granulating process; (2) to select a suitable method of tabletting for sustaining the release of ketoprofen for 12 hr; (3) to perform stability studies according to International Committee on Harmonization (ICH) guidelines and photostability on ketoprofen SR tablets; (4) to study the influence of the storage conditions on release kinetics and melting endotherm of ketoprofen; and (5) to predict the shelf-life of the ketoprofen SR tablets. Tabletting ingredients were ketoprofen, anhydrous dicalcium phosphate, Carbopol 971P, talc, and magnesium stearate. Carbopol 971P solution (0.8% w/v) was used as a granulating solution in the fluid bed granulator. For comparative evaluation, tablets were also prepared by direct compression and wet granulation, and subjected to dissolution. Tablets prepared by fluid bed granulation technique were stored in incubators maintained at 37, 40, 50, and 60 degrees C, 40 degrees C/75% RH, 30 degrees C/60% RH, and 25 degrees C/60% RH, and in a light chamber with light intensity of 600 ft candle at 25 degrees C. Melting endotherms were obtained for the drug as well as the tablets during stability studies by differential scanning calorimetry. Tablets prepared by fluid bed granulation technique prolonged the release of ketoprofen better than tablets obtained by direct compression and wet granulation. Further, it complied with the requirements of ICH guidelines for stability testing. Higher temperature and humidity (40 +/- 2 degrees C/75% RH, 40 degrees C, 50 degrees C, and 60 degrees C) adversely affected the rate and extent of the dissolution. Ketoprofen SR tablets stored in amber-colored bottles demonstrated a good photostability for 6 months at 600 ft candle. The shelf-life of the formulation was predicted as 32 months.