Cellulose acetate phthalate or Cellulose Acetophthalate is a chemical compound, one of tge most effective and most widely used polimers for pH controlled release.
The name defines the structure of the molecule:
- Cellulose is the basic molecule, a polysaccharide consisting of a linear chain of different hundreds or thousands of D-glucose units linked by β(1→4).
- Acetate refers to the acetyl groups attached to some hydroxyl groups in the cellulose molecule. The acetyl group is a functional group derived from acetic acid, with formula -COCH3.
- Phthalate refers to the phthalate groups attached to certain hydroxyl groups of the cellulose molecule. A phthalate group is a functional group derived from phthalic acid, with the formula -C6H4(COOH)2.
The synthesis process takes place in different steps:
- Preparation. Cellulose is a natural polymer found in the cell walls of plants. It can be extracted from wood or cotton pulp through a process involving the removal of non-cellulosic impurities, typically using a combination of mechanical and chemical treatments.
- Acetylation. Cellulose is reacted with acetic anhydride in the presence of a catalyst such as sulfuric acid. This process introduces acetate groups onto cellulose molecules, forming cellulose acetate.
- Phthalation. Cellulose acetate reacts with phthalic anhydride. This introduces phthalate groups onto cellulose acetate, forming cellulose acetate phthalate.
It occurs as a fine vwhite power.
What it is used for and where
Medical
An active pharmaceutical excipient, an anionic polymer composed of phthalic acid and acetate used in medicine to obtain sequential release of drugs, biomolecules, peptides and proteins and has a bacteriostatic effect (1), functions as a stabilizing agent in the preparation of Pseudolatex, a colloidal dispersion useful for encapsulation and controlled drug release.
It is used in oral tablets where it is allowed up to 70mg per tablet (2).
It also has a microbicidal and inactive HIV-1 effect, herpes simplex 1 and 2 and cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi and Chlamydia trachomatis in vitro (3).
Cellulose Acetophthalate or Phthalate Cellulose Acetate has been used for decades as enteric coating films in oral pills, such as Aspirin. It has proven to possess a powerful antiviral activity and an efficacy against herpes (4).
It produces phthalic acid and acetic acid as hydrolysis products, it has a delayed action to acids (5).
Micronized, has proven to be the only microbial candidate with the ability to rapidly remove HIV-1 adsorption from physiological fluids and make the virus non-infectious (6). In addition, it did not interfere with the CD4 binding virus. Since CD4 is the primary cell receptor for HIV-1, it was interesting to study its HIV-1 binding and its consequences, including variations in glycoprotein gp41 conformation within viral particles (7).
Oral drug delivery is always the preferred form of delivery. The main problem with oral drug delivery is first pass metabolism. This becomes a major problem when drug needs to reach to the lower part of the gastrointestinal tract. To overcome this problem, targeted drug delivery systems are being developed. The aim of the research was to give a site and time controlled drug delivery to colon. To achieve this aim, a compression coated drug delivery system containing chitosan and cellulose acetate phthalate was designed and optimized (8).
A simple composite electrospun nanofiber of cellulose acetate phthalate (CAP)-polyethylene glycol (PEG) loaded with tetrahydrocurcumin (THC) was developed in this study, and the in vitro diffusion of THC was evaluated. The nanofibers were characterized by scanning electron microscopy, powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). The formulated nanofiber (NF) with THC has smooth morphology with diameter of around 300-500 nm. The complete entrapment and dispersion of THC was observed from the results of PXRD and DSC due to the loss of THC crystalline property. Further, FT-IR demonstrated that the vibration bands for the polymers used were dominant over the THC, and the vibrational bands of THC were not observed from the final formulation. The drug entrapment by the final CAP + PEG NF was found to be 95.5% with the high swelling index. From the in vitro release study, it was found that the formulated THC-loaded CAP + PEG NF has followed anomalous mechanism, demonstrating both diffusion and swelling controlled modes. The drug release extended up to 12 h with a final cumulative release of 94.24% (9).
Cosmetics
Film-forming agent. It produces, upon application, a very thin continuous film with an optimal balance of cohesion, adhesion and stickiness on skin, hair or nails to counteract or limit damage from external phenomena such as chemicals, UV rays and pollution.
The most relevant studies on this chemical compound have been selected with a summary of their contents:
Cellulose acetate phtalate studies
Typical optimal characteristics of Cellulose acetate phthalate as commercial product :
| Appearance | White amorphous powder |
| Solubility (Turbidity) 5% solution in Acetone | Clear to slight opalescent |
| Solubility (Colour) 5% solution in Acetone | Colourless |
| Sulphated Ash | max. 0.1% |
| Acetyl content | 19 - 24% |
| Phthalyl content | 30 - 36% |
| Acidity (C8H6O4) | max. 3% |
| Water (KF) | max. 5% |
- Molecular Formula: C116H116O64
- Molecular Weight: 2534.12
- CAS: 9004-38-0
- MDL number MFCD00072769
- NACRES SB.52
Safety data sheet
References___________________________________________________________________
(1) Raiche AT, Puleo DA. Association polymers for modulated release of bioactive proteins. IEEE Eng Med Biol Mag. 2003 Sep-Oct;22(5):35-41. doi: 10.1109/memb.2003.1256270.
(2) DMayhew JW, Gideon LT, Ericksen B, Hlavaty JJ, Yeh SM, Chavdarian CG, Strick N, Neurath AR. Development of a gel permeation chromatographic assay to achieve mass balance in cellulose acetate phthalate stability studies. J Pharm Biomed Anal. 2009 Feb 20;49(2):240-6. doi: 10.1016/j.jpba.2008.10.039.
Abstract. Cellulose acetate phthalate (CAP, cellulose acetate 1,2-benzenedicarboxylate) is a common polymeric oral tablet coating. CAP is also a vaginal microbicide candidate that potently inhibits HIV-1 proliferation. This paper describes the development of a precise, stability-indicating gel permeation chromatography (GPC) assay for CAP. During accelerated stability studies monitored by separate reversed-phase high performance liquid chromatography (RP-HPLC) and GPC analyses, an apparent loss of mass balance was observed. This deficit was corrected by recalculating the response factor (RF) for each degraded sample, proportional to the fraction of phthalate remaining bound to the polymeric CAP. The correction factor enabled CAP and the degradation product phthalic acid (PA) to be quantitated by a single GPC analysis. The chromatographic approach taken here could potentially apply to any polymer containing degradable chromophores.
(3) Hadgraft J., Guy R.H. Transdermal Drug Delivery: Developmental Issues and Research Initiatives. Marcel Dekker Eds; New York: 1989. p. 324
(4) Ravikumar R, Ganesh M, Ubaidulla U, Young Choi E, Tae Jang H. Preparation, characterization, and in vitro diffusion study of nonwoven electrospun nanofiber of curcumin-loaded cellulose acetate phthalate polymer. Saudi Pharm J. 2017 Sep;25(6):921-926. doi: 10.1016/j.jsps.2017.02.004.
Abstract. Novel curcumin (CUR)-loaded cellulose acetate phthalate (CAP) nonwoven electrospun nanofiber (NF) transdermal mat was developed and evaluated for its in vitro CUR diffusion properties. Various CAP solutions from 5 to 20 wt% were tested; 17.5 wt% was found to be a suitable concentration for NF fabrication without defects, such as bubble or ribbon structures. The selected wt% CAP solution was loaded with CUR and electrospun into NFs. The prepared CUR-loaded NFs were characterized using scanning electron microscopy, X-ray diffraction, ultraviolet-visible spectroscopy, thermogravimetric analysis (TGA), and in vitro diffusion studies. The as-prepared fibers demonstrated controlled in vitro transdermal delivery of CUR for up to 24 h.
(5) Jagdale S, Chandekar A. Optimization of Chitosan and Cellulose Acetate Phthalate Controlled Delivery of Methylprednisolone for Treatment of Inflammatory Bowel Disease. Adv Pharm Bull. 2017 Jun;7(2):203-213. doi: 10.15171/apb.2017.025.
Abstract. Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life-long disorder. The best way to tackle IBD is to develop a site targeted drug delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. The aim of the present research was to develop a colon targeted drug delivery for treatment of IBD. Methods: Compression coated drug delivery system was designed and optimised. Core tablet contained drug, croscarmellose sodium (CCS-superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of experiment with 32 factorial design was applied for optimization of compression coated delivery. Chitosan and cellulose acetate phthalate were chosen as independent variables. Swelling index, hardness and % drug release were dependant variables. Results: Core tablet (C5 batch) containing 2.15% CCS showed disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of any significant physical and chemical interaction between drug and polymers. F8 was found to be optimised formulation. F8 contained 35% chitosan and 17.5% cellulose acetate phthalate. It showed drug release of 86.3% ± 6.1%, hardness 6.5 ± 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 ± 8.6% with 7.5 hrs lag time. The results confirmed that the lag time was highly affected by the coating of the polymers as well as the concentration of the superdisintegrant used in core tablet. Conclusion: In-vitro and in-vivo results confirmed a potential colon targeted drug therapy for treatment of IBD.
(6) Neurath AR, Strick N, Li YY, Lin K, Jiang S. Design of a "microbicide" for prevention of sexually transmitted diseases using "inactive" pharmaceutical excipients. Biologicals. 1999 Mar;27(1):11-21. doi: 10.1006/biol.1998.0169.
Cellulose acetate phtalate 
Phtalic acid
