QUALITY CONTROL OF PEPTIDE/ PROTEIN  BASED PRODUCTS-  

To ensure efficacy and safety of a drug product, the active compound and its degraded product(s) must be quantified to determine the expiry period of the formulation. Due to the multiplicity of protein degradation pathways, no single test method can be guaranteed to be stability indicating. Only the continued information from various methods can lead to the assurance that the physicochemical integrity and biological activities of a protein are retained throughout manufacturing and shelf life. 

Peptide degradation have been reported as result of the following reasons-  

- Thermal denaturation (heat as well as cold)

- pH denaturation

- Salt denaturation

- Pressure and shear denaturation

- Surface denaturation and

- Freeze drying denaturation 

In addition to monitoring the integrity of the protein primary structure, protein conformation stability at secondary, tertiary and quaternary levels must also be verified to assure maintaining biological function.  

REGULATORY CONSIDERATIONS-  

Internationally, biotechnology products are regulated under the statutory authority of four federal agencies: the Food and Drug Administration, The Environmental Protection Agency, the Occupational Safety and Health Administration and the United Nations department of Agriculture. 

Unlike conventional drugs, peptides and protein drugs have primary, secondary and tertiary structures, all of which must be taken into account in order to gain complete control of the identity, strength, quality and potency of the material. As a result of this, establishing specific standards for the identity, strength, quality, potency and stability of peptide and protein drugs is a complex procedure; the use of the recombinant DNA (rDNA) techniques or hybridoma manufacturing process to produce peptides and proteins introduces additional complexities. 

CONCLUSION-  

Mucosal adhesive dosage forms are now at the starting line. The advantages are tremendous, which make further study in this field extremely important. The formulation of these drug delivery systems depends on the development of suitable polymers bearing excellent mucoadhesive properties, characteristics, size and molecular weight of peptides, their stability individually and in presence of mucoadhesive polymers and the overall biocompatibility of the dosage form. Obviously as the pharmaceutical industry moves into the area of peptide-based therapies, there will be greater stimulus for development of mucosal and like novel technologies of drug delivery.

For clarifications, please contact us at 1-514-743-6159 or email at contact@innoworksltd.com

 

 

Methods used to study mucoadhesion: 

Several test methods have been reported for studying mucoadhesives. These tests are necessary not only to screen a large number of candidate mucoadhesives, but also to study their mechanisms. These tests are also important during the design and development of a bioadhesive modified release system as they ensure compatibility, physical and mechanical stability, surface analysis and bioadhesive bond strength. The test methods can broadly be classified into two major categories: 

1. In vitro/ ex vivo methods; including: 

            - Measurement of tensile strength

            - Measurement of shear strength

            - Adhesion weight method

            - Fluorescent probe method

            - Flow channel method

            - Spectroscopic method

            - Falling liquid film method

            - Colloidal gold staining method

            - Viscometric method

            - Thumb test.

            - Adhesion number evaluation

            - Electrical conductance

 2. In vivo methods:

In vivo techniques for measuring bioadhesive strength are relatively few. Some of the reported methods are based on the measurement of the residence time of bioadhesives at the application site. The gastrointestinal transit time of many bioadhesives have been examined using radioisotopes. 

Bio/ Muco adhesive polymers: 

Polymers that adhere to the mucin- epithelial surface can be conveniently divide into three broad categories: 

1. Polymers that become sticky when placed in water and owe their bioadhesion to stickiness. 

2. Polymers that adhere through non-specific, noncovalent interactions, which are primarily electrostatic in nature. 

3.  Polymers that bind to specific receptor sites on the cell surface. 

All three-polymer types can be used for drug delivery. 

Characteristics of an ideal mucoadhesive polymer: 

The ideal polymer for a mucoadhesive drug delivery system should have the following characteristics: 

1. The polymer and its degradation products should be nontoxic and nonabsorbable from the gi tract. 

2. The polymers should be nonirritant to the mucous membrane. 

3. It should preferably form a strong noncovalent bond with the mucin- epithelial cell surface. 

4. It should adhere quickly to moist tissue and should possess some site specificity.

5. It should allow easy incorporation of the drug and offer no hindrance to its release.

6. The polymer must not decompose on storage or during the shelf life of the dosage form. 

7. The cost of the polymer should not be high, so that the prepared dosage form remains competitive. 

Several polymers viz. carbomers, celluloses e.g. sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, hydroxy ethyl cellulose etc., guar gum, sodium alginate, polycarbophils etc. are being studied as potential mucoadhesice agents.

For clarifications, please contact us at 1-514-743-6159 or email at contact@innoworksltd.com

The rational approach for developing innovative polypeptide delivery system must therefore initially address two basic questions: 

1.      What is the rate & time course of systemic drug input (i.e. the input function i(t) that will maximize the therapeutic effect of the compound, minimize side effects and prevent if possible the development of tolerance (tachyphylaxis)?   And 

2.      What routes of administration (and associated pharmaceutical technologies) will provide the best means for achieving this input function in a safe, efficacious, reliable, “patient friendly” and cost-effective manner ? 

The following equation provides a simple theoretical framework for assessing the rate limiting steps responsible for the bioavailability (F) of polypeptides given by the transmucosal route:

 

F  =[            TLM         ]           [               TM   ____]

            TLM + DL + EL          TMB  +  DM

Where in, 

L =       human, M   =   mucosa, B  =  bloodstream, EL  =Elimination from absorption site (pre absorption clearance) 

This mechanistic information is valuable for selecting appropriate routes of administration as well as for developing rational strategies to enhance the bioavailability.

Factors governing mucoadhesion:

The bioadhesive power of a polymer or a series of polymers is affected by the nature of the polymer and also by the nature of the surrounding media:

1. Polymer related factors: 

            - Molecular weight

            - Concentration of the active polymer

            - Flexibility of polymer chains

            - Spatial conformation

            - Polymer swelling index.

2. Environmental related factors:

            - pH

            - Applied strength of adhesives

            - Initial contact time

            - Selection of model substrate surface

            - Concentration of water or water content in substrate

3.Physiologic variables:

            - Mucin turn over

            - Disease state

            - Histology of organ (epithelial tissue)

In the next chapter we shall discuss on techniques used to study muco-adhesion.

For clarifications, please contact us at 1-514-743-6159 or email at contact@innoworksltd.com 

Mucoadhesive drug delivery systems utilize the property of bioadhesion of certain water-soluble polymers, which become adhesive on hydration and hence can be used for targeting a drug to a particular region of the body for extended periods of time.

 

The mucosal layer lines a number of regions of the body including the gastrointestinal tract, the urinogenital tract, the airways, the ear, nose and eye. These represent potential sites for attachment of any bioadhesive system and hence, the mucoadhesive drug delivery system may include the following:

 

1. Buccal and other trans- oral delivery system.

2. Pulmonary delivery system.

3. Vaginal delivery system.

4. Rectal delivery system.

5. Nasal delivery system.

6. Ocular delivery system.

7. Colonic delivery system and

8. Gastrointestinal delivery system. 

 

Rationale for mucosal delivery system of peptides:

 

The idea of mucoadhesives was derived from the need to localize drugs at a certain site in the body. Often the extent of drug absorption is limited by the residence time of the drug at the absorption site.

 

For example, in ocular drug delivery, less than 2 min are available for drug absorption after instillation of a drug into the eye, since it is removed rapidly by solution drainage; hence the ability to extend contact time of an ocular drug delivery system in front of the eye would undoubtedly improve drug bioavailability.

 

In oral drug delivery the drug absorption is limited by the gastrointestinal transit time of the dosage form. Since many drugs are absorbed only from the upper small intestine, localizing oral drug delivery in the stomach or in the duodenum as well as colon targeting for drugs, which degrade in gastric environment, would significantly improve the extent of drug absorption.

 

Since most of the routes of drug administration such as ocular, nasal, buccal, respiratory, gastrointestinal, rectal etc. are coated with the mucus layer, mucoadhesives are logically expected to increase the residence time. In addition, they provide intimate contact between a dosage form and the absorbing tissue, which may result in high drug concentration in a local area and hence high drug flux through absorbing tissue. Furthermore, the intimate contact may increase the total permeability of high molecular weight drugs such as peptides and proteins.

 

Since, peptides are highly susceptible to the strong acid environment and the proteolytic enzymes in the gastro-intestinal tract (gi tract), the systemic bioavailability therefore by the conventional oral administration is extremely low. Peptides are high molecular weight macro molecules (100-150,000 Da) and thus do not easily permeate the intestinal mucosa. Even after successful gastrointestinal absorption, they are further subjected to first pass elimination in the liver. Thus, conventional oral route of delivery produces sub-therapeutic drug levels in the body.  For these reasons, even the smallest peptide may demand new pharmaceutical principles for the development of a satisfactory product.

 

In the next chapter we shall discuss further on the rationale approach in the development of mucosal drug delivery systems. 

For clarifications, please contact us at 1-514-743-6159 or email at contact@innoworksltd.com

 

For additional reading on mucosal DDS, in my next chapter, I shall present a list of references that may be useful to give more insight into this delightful topic. 

Jeng, M. J., Lee, Y. S., & Soong, W. J. (2007). Effects of perfluorochemicals for intrapulmonary vancomycin administration and partial liquid ventilation in an animal model of meconium-injured lungs. Acta Paediatrica Taiwanica, 48, 309-316.

Leary, S., Liu, C., & Apuzzo, M. (2006). Toward the emergence of nanoneurosurgery: Part II--Nanomedicine: Diagnostics and imaging at the nanoscale level. Neurosurgery, 58, 805-823.

Maloney, J., Uhland, S., & Polito, B. (2005). Electrothermally activated microchips for implantable drug delivery and biosensing. Journal of Controlled Release, 109, 244 255.

Medscape Medical News. (2002). 'Pain relief ball' cuts opioid use after gynecologic surgery. Retrieved on March 16, 2008, from http://wwwmedscape.com/viewarticle/433317

Morrow, J., Bawa, R., & Wei, C. (2007). Recent advances in basic and clinical nanomedicine. Medical Clinics of North America, 91,805 843.

Nova Science Now. (n.d.). Cancer nanotech. Retrieved May 10, 2008, from http://www.pbs.org/wgbh/nova/sciencenow/3209/ 03-canc-nf.html

Skryabina, E., & Dunn, T. (2006). Disposable infusion pumps. American Journal of Health System Pharmacists, 63, 1260 1268.

Tasciotti, E., Liu, X., & Bhavane, R. (2008). Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nature Nanotechnology, 3, 151 157.

Triangle Business Journal. (2008, May). BDSI's pain patch does well in human trial. Retrieved May 30, 2008 from http:// triangle.bizjournals.com/triangle/stories/2008/05/05/daily28. html

Wermeling, D. P, Miller, J. L., & Rudy, A. C. (n.d.). Systemic" Intranasal drug delivery: concepts and applications. Drug Delivery Technology. Retrieved March 16, 2008, from http://www. drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=22

Wynne, A. L., Woo, T. M., & Olyaei, A. J. (2007). Pharmacotherapeutics for nurse practitioner prescribers (2nd ed.). Philadelphia: EA. Davis.

Yih, T., & Al-Fandi, M. (2006). Engineered nano particles as precise drug delivery systems. Journal of Cellular Biochemistry, 97, 1184-1190.

Young, E. (2004). Drug-delivering contact lenses revealed. NewScientist.com news service. Retrieved June 1,2008, from http://newsscientist.com/article.ns?id=dn6597

Angelia Colwell Berkowitz, BSN RN CRNI, is a graduate student at The University of Texas Health Science Center at San Antonio, San Antonio, TX.  

The next series shall comprise of the formulation challenges as well as quality considerations and regulatory challenges faced during the development of mucosal DDS.  

For an expert opinion on formulation development of peptide/ protein molecules, please contact us at 1-514-743-6159 or email contact@innoworksltd.com 

For additional reading on mucosal DDS, in my next chapter, I shall present a list of references that may be useful to give more insight into this delightful topic. 

De Campos A.M.;Diebold Y.;Carvalho E.L.S.;Sánchez A.,José Alonso M. Chitosan nanoparticles as new ocular drug delivery systems: in vitro stability, in vivo fate, and cellular toxicity. Pharmaceutical Research, Springer. 2004; 21(5): 803-810(8).  

Alvarez-Lorenzo, C., Hiratani, H., & Concheiro, A. (2006). Contact lenses for drug delivery: Achieving sustained release with novel systems. American Journal of Drug Delivery, 4, 131-151.

American Heart Association. (2005). Management of cardiac arrest recommended by the American Heart Association. Retrieved June 23, 2008, from http://circ.ahajournals.org/cgi/ content/full/112/24_suppl/IV-58

Bajwa, Z., & Warfield, C. (2008). Interventional approaches to the management of cancer pain. Retrieved on May 13, 2008, from www.uptodate.com

Bielinska, A., Janxzak, K., & Landers, J. (2008). Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Thl polarized responses and neutralizing antibodies to primary HIV type isolates. AIDS Research and Human Retroviruses, 24, 271-281.

Bulletin Board. (2008). Nanomedicine, 3, 145-147.

Canadian Press. (2008). Canadian researchers develop automated anesthesia system dubbed McSleepy. Retrieved May 6, 2008, from www.googlenews.com

Chandhari, M., & Mackenzie, P. (2007). Implantable technology for pain management. Anaesthesia & Intensive Care Medicine, 9, 69-74.

Clinical Trials. (2008, February). BioDelivery sciences to present BEMA fentanyl data at the 24th Annual Meeting of the American Academy of Pain Medicine. Retrieved on May 15, 2008, from http://www.drugs.corn/clinical_trials/biodeliverysciences-present- bema-fentanyl-data-24t

Cox, C. (n.d.). Treatment options gel with innovative drug delivery systems. Drug Delivery Technology Retrieved on May 16, 2008, from http://www.drugdeliverytech.com/cgi-bin/articles. cgi?idArticle=55

Gotfried, M. H., Shaw, J. P., Benton, B. M., Krause, K. M., Goldberg, M. R., Kitt, M. M., et al. (2008). Intrapulmonary distribution of intravenous televancin in healthy subjects and effect of pulmonary surfactant on in vitro activities of televancin and other antibiotics. Antimicrobial Agents and Chemotherapy, 52, 92-97.

Hafeli, U. (2004). Magnetically modulated therapeutic systems. International Journal of Pharmaceutics, 277, 19-24.

Hirlekar, R., Patel, P, & Dand, N. (2008). Drug loaded erythrocytes: As novel drug delivery system. Current Pharmaceutical Design, 14, 63 70.

in-Pharma Technologist.com. (January 10, 2005). Contact lenses deliver drugs to eye. Retrieved on May 30, 2008, from http:// www.in-pharmatechnologist.com/news/ng.asp?id=57187-contact-lenses-deliver

Irani, F., Dankert, M., Brensinger, C., Bilker, W., Nair, S., Kohler, C., et al. (2004). Patient attitudes towards surgically implantable, long-term delivery of psychiatric medicine. Neuropsychopharmacology, 29, 960-968.

For an expert opinion on formulation development of peptide/ protein molecules, please contact me at  1-514-743-6159 or email contact@innoworksltd.com

For additional reading on mucosal DDS, in my next chapter, I shall present a list of references that may be useful to give more insight into this delightful topic. 

M.S. El-Samaligy, N.N. Afifi, E.A. Mahmoud .Increasing bioavailability of silymarin using a buccal liposomal delivery system: Preparation and experimental design investigation. International Journal of Pharmaceutics 2006; 308:140–148.  

Libero Italo Giannola , Viviana De Caro , Giulia Giandalia ,Maria Gabriella Siragusa , Claudio Tripodo , Ada Maria Florena , Giuseppina Campisi . Release of naltrexone on buccal mucosa: Permeation studies, histological aspects and matrix system design. European Journal of Pharmaceutics and Biopharmaceutics. 2007.  

Ana Figueiras , Rui A. Carvalho , Laura Ribeiro , Juan J. Torres-Labandeira Francisco J.B. Veiga .Solid-state characterization and dissolution profiles of the inclusion complexes of omeprazole with native and chemically modified b-cyclodextrin.ssuropean Journal of Pharmaceutics and Biopharmaceutics. 2007.

Axel Schneeweis, Christel C. Muller-Goymann. Controlled release of solid-reversed-micellar-solution (SRMS) suppositories containing metoclopramide-HCl. International Journal of Pharmaceutics. 2000; 196:193–196.  

Ulrich Klotz, Matthias Schwab .Topical delivery of therapeutic agents in the treatment of inflammatory bowel disease. Advanced Drug Delivery. 2005; 57:267-279.  

ST Lim, B Forbes, GP Martin, and MB Brown. In vivo and in vitro characterization of novel micro particulates based on hyaluronan and chitosan hydroglutamate.AAPS PharmSciTech2001; 2 (4). 

Sambhaji Pisal, Vijay Shelke, Kakasaheb Mahadik,Shivajirao Kadam. Effect of organogel components on in vitro nasal delivery of propranolol hydrochloride. AAPS PharmSciTech 2004; 5 (4) Article 63.  

E. Gavini , A.B. Hegge , G. Rassu a, V. Sanna , C. Testa ,G. Pirisino , J. Karlsen , P. Giunchedi.Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies. International Journal of Pharmaceutics .2006; 307:9-15.  

Sonal R. Patel , Hui Zhong , Ashutosh Sharma , Yogeshvar N. Kalia. In vitro and in vivo evaluation of the transdermal iontophoretic delivery of sumatriptan succinate.European Journal of Pharmaceutics and Biopharmaceutics.2007; 66: 296–301.  

Hongxia Lin , Matthias Gebhardt , Shengjie Bian , Kyoung Ae Kwon ,Chang-Koo Shim, Suk-Jae Chung, Dae-Duk Kim. Enhancing effect of surfactants on fexofenadine·HCl transport across the human nasal epithelial cell monolayer. International Journal of Pharmaceutics.2007; 330:23–31.  

Jean-Louis Bourges, Sandrine E. Gautier, Florence Delie, Riad A. Bejjani, Jean-Claude Jeanny, Robert Gurny, David Ben Ezra, and Francine F. Behar-Cohen.Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticses. Investigative Ophthalmology and Visual Science. 2003; 44:3562-3569. 

For an expert opinion on formulation development of peptide/ protein molecules, please contact me at 1-514-743-6159 or email drshrutibhat@gmail.com

For additional reading on mucosal DDS, in my next chapter, I shall present a list of references that may be useful to give more insight into this delightful topic. 

References: 

Shruti Bhat, review artcile, Chemical weekly, 1997. 

www.allbusiness.com / pharmaceutical-biotechnology. 

Brahmankar D. M., Jaiswal S. B. Controlled Release Medication in Biopharmaceutics and Pharmacokinetics a Treatise. 1st edition, Vallabh Prakashan, Delhi, 1995; 335-371.  

Lachman Leon, Lieberman H. A., Kanig J. L.The Theory and Practice of Industrial Pharmacy. 3 rd ­ edition, Varghese Publishing House, Bombay, 1987; 430-456. 

Chien Y. W. Novel drug Delivery Systems. Marcel Dekker, 1982; 171-177.  

A J Moës.Gastric retention system for oral drug delivery. Drug Delivery Oral.2005. http://www.bbriefings.com/pdf/890/PT04_moes.pdf.  

Jian-Hwa Guo, PhD ,Carbopol polymers for pharmaceutical drug delivery applications. Excipient Updates. Drug Delivery Technology. http://www.drugdeliverytech.com/cgi-bin/articles.cpi?idArticle=159.  

Seham S. Abd E Hady, Nahed D. Mortada, Gehanne A. S. Awad, Noha M. Zaki, Ragia A. Taha. Development of in situ gelling and mucoadhesive mebeverine hydrochloride solution for rectal administration. Saudi Pharmaceutical Journal. 2003; 11(4):159-171.

Khalid U. Shah, PhD & Jose G. Rocca, PhD. Lectins as next generation mucoadhesive for specific targeting of the gastrointestinal tract. Gastrointestinal Targeting, Drug Delivery Technology. http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=245.  

Kok Khiang Peh, Choy Fun Wong. Polymeric films as vehicle for buccal delivery: Swelling, mechanical and bioadhesive properties. Journal of Pharmacy and Pharmaceutical Sciences. 1999; 2(2):53-61.  

Kashappa Goud, H. Desai, and T.M. Pramod Kumar.Preparation and evaluation of a novel buccal adhesive system.AAPS PharmSciTech. 2004; 5(3):article 35.  

Joe McDonough and Wade Schlameus.Uncontrolled growth of controlled selease drug delivery technology and markets. Pharmaceutical Research and Microencapsulation Specialists at the Southwest Research Institute.  

Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and Sotira Chaitidou.Recent advances in novel drug delivery systems. Azojono Journal Of Nanotechnology.2006; 10:2240/1110.  

Woodley, John .Bioadhesion: New Possibilities for Drug Administration. Leading Article.Clinical Pharmacokinetics. 2001; 40(2):77-84.  

Juan Manuel Llabot, Ruben Hilario Manzo and Daniel Alberto Allemandi. Double-layered mucoadhesive tablets containing nystatin. AAPS PharmSciTech 2002; 3 (3) article 22  

K.P.R. Chowdary and Y. Srinivasa Rao .Design and in vitro and in vivo evaluation of mucoadhesive microcapsulesof glipizide for oral controlled release: a technical note. AAPS PharmSciTech 2003; 4 (3) Article 39.

For an expert opinion on formulation development of peptide/ protein molecules, please contact me at  1-514-743-6159 or email contact@innoworksltd.com   

The enzymatic activities associated with the micro flora of colon can be used as a tool for colon specific drug delivery. The large intestine has been appreciated as a promising site for the administration of poorly absorbable drug molecules for their improved bioavailability following oral administration. The colon is known to have somewhat lesser diversity and intensity of enzymatic activities as compared to stomach and small intestine. In addition, the colon has a longer retention time and appears to be highly responsive to agents that enhance the absorption of poorly absorbed drugs. 

The site-specific delivery of drugs to the colon has implications in a number of areas which include-

1. Local treatment and irradication of colonic diseases.
2. For delivering peptides and proteins through oral route (colon targeted products).
3. In the improvement of therapy in diseases susceptible to diurnal rhythm.

1. An outer film, which recognizes if the system has left the stomach.
2. An intermediate layer which swells (based on hydrophilic swellable polymer) following the outer film, which dissolves in the small intestine. This layer has to protect the core during the small intestine transit (at least 3-4 hours).
3. An additional layer between the swellable polymer and core is casted in order to deter premature release of contents.

1. Delivery rate to colon
2. Lipid solubility
3. Colonic residence, site of absorption in colon (proximal or distal)
4. pH / pKa of drug
5. Micro flora climate of colon
6. Mucous barrier
7. Mucosal pore size and permeability index
8. Concentration of drug Vs colon contents

1. Studies with colonic tissues including colonic slices, segments, isolated mucosa, human colonic organ culture.
2. Studies with cellular preparations
3. Studies with sub cellular preparations viz. using coenzyme, cell fractionation isolate mitochondria and studying metabolism kinetics. 

1. Radiolabeling: gamma scintigraphy or neutron activation analysis.
2. Gamma camera imaging.
3. Telemeric capsule.
4. Colonoscopy.
5. Artificial stroma.

Rectal delivery of peptides and protein drugs is another very active area of research. Rectal delivery offers many advantages including-

1. Avoidance of drug absorption prior to reaching the systemic circulation and of drug contact with digestive fluids and consequential degradation.
2. The rate of drug absorption via. the rectum is not influenced by ingestion of food or the rate of gastric emptying.
3. Reduction in first - pass metabolism.
4. Rapid systemic absorption by administering the drug rectally in a suitable solution form.
5. Safe and convenient especially for infants and children.
6. Drug absorption can be interrupted in case of accidental overdose or drug reaction.

1. Factors affecting drug availability rectally-

1. Rectal fluid-
2. Amount
3. Composition
4. pH
5. Buffer capacity
6. Surface tension
7. Viscosity
8. Luminal pressure

 2. Drug substance-

1. Solubility
2. Surface properties
3. Particle size
4. Drug concentration
5. pKa

 3. Vehicle-

1. Composition
2. Fusion behavior
3. Surface tension
4. Rheological behavior.

 The extent of breakdown of peptides is low in the lower digestive tract relative to the small intestine and the stomach, due to low enzymatic activity and neutral pH. Reports on peptide and protein drugs delivered by the rectal route include insulin, calcitonin, gastrin, pentagastrin, human growth hormone and vassopressin.

In the next chapter, let us discuss mucosal DDS by the colon-targeted route.

For an expert opinion on formulation development of peptide/ protein molecules, please contact me at 1-514-743-6159 or email contact@innoworksltd.com