5. COMPOUNDING IN HOSPITALS

COMPOUNDING IN HOSPITALS: A TEACHER’S COMPREHENSIVE GUIDE

Welcome, future hospital pharmacists and compounding professionals!

Compounding of drugs is a process used by a pharmacist or physician to combine, mix, or change various drug ingredients to develop a medication that fulfils the specific needs of a patient for whom an approved drug may be inappropriate—for example, due to an allergy to a dye present in the product. Compounding pharmacists prepare sterile drugs that are regularly used in hospitals, such as eye drops, injections, and IV bags. Depending on the type and quality of drugs to be prepared, compounding is performed either manually or through automation and robotics, each with its own benefits and drawbacks.

As a pharmacy educator with years of experience teaching hospital pharmacy and compounding, I have observed that students often underestimate the complexity and importance of pharmaceutical compounding. Compounding is not just about mixing ingredients—it is about ensuring sterility, accuracy, stability, and patient safety. A single error in compounding can have devastating consequences for a patient.

In this comprehensive guide, I will walk you through the principles of bulk compounding, IV admixture services, and total parenteral nutrition (TPN). By the end of this article, you will have a thorough understanding of the control systems, requirements, preparation methods, and safety considerations involved in hospital compounding. Let us begin our journey into the critical field of pharmaceutical compounding.

Dpharmguru’s exam insights:

Compounding in hospitals is a frequently tested topic in pharmacy exams. Remember: Bulk compounding is defined by the FDA as “the combination, mixing or alteration of drug ingredients to create medications to fulfil the need of patient.” Key concepts include: manufacturing process control, quality control, budgetary control, and the requirements for bulk compounding. IV admixture services and TPN are also important topics—pay special attention to incompatibilities and the role of the pharmacist!

5.1. BULK COMPOUNDING

Bulk compounding is defined by the FDA as the combination, mixing, or alteration of drug ingredients to create medications to fulfil the need of the patient. It is a bulk drug or active pharmaceutical ingredient of product, in bulk form.

These programmes are developed for the preparation of non-commercially available drugs and modified formulations to be used clinically or for investigation. The decision of manufacturing or purchasing drugs depends on several factors, including control systems for bulk compounding, requirements for bulk compounding, and maintenance of manufacturing equipment.

5.1.1. Control Systems for Bulk Compounding

1. Manufacturing Process Control

A hospital pharmacist develops a product to meet pharmaceutical standards. Adequate manufacturing controls lead to products with precise identity, strength, purity, and quality. Adequate packaging and labelling controls prevent mix-up of products, packages, and labels.

2. Quality Control

Quality control indicates measures through which it may be decided whether or not a developed product is meeting the established standards. Quality control in the pharmacy department is of the following categories:

• Quality control of raw materials
• Quality control of instruments used
• Quality control of area to ensure specified pharmaceutical environment
• Quality control of finished products

3. Budgetary Control

Budgetary control regulates the economic aspects of the hospital pharmacy manufacturing programme. An adequate budgetary control over the manufacturing programme can be developed if the hospital pharmacist gives lengthy consideration to inventory and consumption rate for the finished product, raw material requirements, manufacturing capacity, available personnel, and operating costs.

5.1.2. Requirements for Bulk Compounding

• Manufacturing Requirements: Assessed in terms of rate or volume of production, batch quantity, or manufacturing frequency. Depends on the probable consumption rate of each item.
• Raw Material Requirements: The hospital pharmacist should arrange for procurement of required supplies, including raw materials, containers, labels, and ancillary materials. The quantity is estimated by different formulae and recorded on a summary sheet.
• Manufacturing Capacity: Depends on the availability of equipment and hospital economy to fulfil the requirement. Automatic, semi-automatic, or manual equipment is available to meet every production need.
• Manufacturing Facilities: Include a maximum degree of cleanliness in aseptic filling rooms, with buffer areas having slightly lower cleanliness standards. Ceilings, walls, and floors should be made of easy-to-clean, non-porous materials.
• Manufacturing Equipment and Sources: Type and size depend on the manufacturing programme—quantities to be produced, duration of production time, availability of physical facilities, and availability of persons.
• Manufacturing Personnel: A technically skilled and legally qualified pharmacist acts as a supervisor. Ancillary personnel constitute the manufacturing staff. The number of staff is critical for economy—excessive personnel raises costs, while insufficient staff may lead to errors.
• Operating Cost: Includes direct cost (labour, cost of material) and indirect or overhead cost (building maintenance, insurance policies, space maintenance, equipment depreciation, and housekeeping).

5.1.3. Maintenance of Manufacturing Equipment

Maintenance of manufacturing equipment is a control over equipment operation. High investment in pharmaceutical manufacturing equipment and expense related to frequent repairs demand an equipment maintenance programme to ensure maximum performance with the lowest repair cost. Development of an equipment maintenance programme is the pharmacist’s responsibility.

Dpharmguru’s exam insights:

Control systems for bulk compounding are frequently tested. Remember the three key controls: Manufacturing Process Control (ensures identity, strength, purity, quality), Quality Control (raw materials, instruments, area, finished products), and Budgetary Control (economic aspects). Also, remember the seven requirements for bulk compounding—manufacturing, raw materials, capacity, facilities, equipment, personnel, and operating costs!

5.2. IV ADMIXTURE SERVICES

5.2.1. Definition

IV admixture is the combination of one or more sterile products added to an IV fluid for administration. It is also defined as a pharmaceutical mixture of two or more drugs into a large bag or bottle of IV fluid. IV admixture is formed by combining one or more sterile products in a 50mL or larger bag or bottle of IV fluid for parenteral administration. IV admixture should be made in a suitable environment using aseptic techniques to maintain its sterility and keep it free from pyrogens and particulate matter.

5.2.2. Advantages of IV Admixtures

• Extend the expiration period
• Time-saving preparation process
• Provide large amounts of nutritive fluids (glucose and electrolytes) and nutrients
• Quick onset of action
• Can be administered to patients who are vomiting or unconscious
• Effective, safe, and high-quality patient care
• Can be used to administer drugs that are poorly absorbed or unstable in the GIT
• Accurate and proper reconstituted drugs

5.2.3. Disadvantages of IV Admixtures

• High risk of incompatibility
• Need skill and time
• Need aseptic area and special storage equipment (e.g., refrigerator)
• Need trained pharmacists
• Risk of bacterial contamination
• Higher risk of causing adverse reactions
• Difficult to maintain IV line

5.2.4. Preparation of IV Admixtures

• After receiving the physician’s original order, prepare a pressure-sensitive label with patient name and address, physician name, drug names with quantities, date of compounding, expiration date, and pharmacist’s name.
• Prepare the admixture under a laminar flow hood using sterile needles and syringes or double-ended transfer needles.
• If reconstitution is needed, follow the manufacturer’s recommendations.
• Add the reconstituted solution immediately to the infusion solution to reduce microbial contamination and prevent degradation.
• Some drugs require specific pH for preparation (e.g., amphotericin should be diluted in glucose infusion with pH >4.2).
• After making additions, mix thoroughly to prevent concentrated layers.
• Replace the metadisc with a new seal crimped—use a different coloured seal for safety.
• Check solutions for particulate matter before use.
• Label with patient name, added drug and quantity, and time/date of addition.
• Check for turbidity, colour change, crystallisation, or other signs of interaction during administration.

5.2.5. Incompatibilities of IV Admixtures

Drug incompatibilities are undesirable reactions that occur due to simultaneous dilution and/or administration of two or more drugs through a single IV line or in a single solution. They hamper therapeutic efficacy and patient safety, visually proven by change of solution colour, precipitation, or turbidity.

Types of IV Admixture Incompatibilities:

• Physical Incompatibility: Occurs when mixing leads to visible changes—change in appearance, colour, or formation of precipitates. Major factors: pH-value and buffer capacity (pKa value) of parenterals.
• Chemical Incompatibility: Occurs when the drug undergoes chemical degradation—oxidation, reduction, hydrolysis, photolysis, decomposition, complexation, or racemisation. Results in decreased active drug and/or toxic byproducts.
• Therapeutic Incompatibility: Occurs when drugs are administered simultaneously, resulting in unwanted antagonistic or synergistic pharmacological action. For example, chloramphenicol antagonises penicillin’s antibacterial effects.

Causes of IV Admixture Incompatibilities:

• Drugs and unsuitable diluents
• Two drugs causing drug-drug incompatibility
• Two or more drugs in the same infusion line or IV container
• Drugs and adjuvants (stabilisers, solvents)
• Drugs and materials of IV containers (e.g., PVC)

Prevention of IV Admixture Incompatibilities:

• Checking for strict indications for each drug preparation
• Separating drug doses by time and place
• Using multi-lumen catheters
• Using appropriate in-line filters
• Reducing the number of drugs mixed together
• Administering solutions soon after mixing
• Referring to compatibility references
• Using freshly prepared solutions
• Discarding unused solution after 24 hours
• Observing the running of IV fluid for appearance changes

5.2.6. Role of Pharmacist in IV Admixture Administration

• Provide permanent supervision and involvement in IV admixture services
• Prepare protocol for IV admixture service and establish reporting error system
• Advise on compatibility and stability for multiple drugs
• Update staff on new clinical practice guidelines
• Prevent unsafe incompatibility using available literature, databases, and services
• Use colour coding to prevent incompatibility
• Prepare individual labelling for each drug preparation
• Use inline filters properly to reduce particle influx

Dpharmguru’s exam insights:

IV admixtures are frequently tested. Remember: Physical incompatibility = visible changes (precipitation, colour change). Chemical incompatibility = chemical degradation (hydrolysis, oxidation, photolysis). Therapeutic incompatibility = unwanted pharmacological effects (antagonism or synergism). The pharmacist plays a crucial role in preventing these incompatibilities through supervision, protocol development, and staff education!

5.3. TOTAL PARENTERAL NUTRITION (TPN)

5.3.1. Definition of TPN

Total Parenteral Nutrition (TPN) is a feeding method that bypasses the GIT. In this method, fluids are administered via the intravenous route to provide maximum nutrients the body needs. TPN is used when a person is unable to or should not receive feedings or fluids orally.

5.3.2. Composition of TPN

TPN is a mixture of all essential nutritional components, including protein, fat, calories, vitamins, and minerals. TPN solutions should be modified as per the need of each patient, depending on their age and state of organ function.

Macronutrients:

• Proteins: A specially prepared mixture of synthetic, essential amino acids is supplied intravenously. 200ml bottles containing 8-9% amino acids are available. Patients with normal hepatic/renal function need 1.5 gm protein/kg/day.
• Calories: Administered as 20-25% dextrose in water through a central vein. 3.4 calories are obtained from one gram of dextrose.
• Fats: Lipids provide calories and prevent Essential Fatty Acid Deficiency (EFAD). Common sources: soybean/safflower oil, egg yolk phospholipids in 10%, 20%, and 30% concentrations. 1.1 calories from 1ml of 10% emulsion.

Micronutrients:

• Vitamins: Thiamine, riboflavin, niacin, biotin, ascorbic acid, cyanocobalamin, etc.
• Trace elements: Copper, zinc, selenium, and chromium (monitored monthly).
• Electrolytes (per litre): Sodium (100-150 mEq), Potassium (50-100 mEq), Magnesium (8-24 mEq), Calcium (10-20 mEq), Phosphorous (15-30 mEq).

5.3.3. Types of TPN

• Central Parenteral Nutrition (CPN): Fluids delivered through a central vein (superior vena cava). A larger catheter can deliver higher concentrations of calorie-rich nutrients. Used for total parenteral nutrition.
• Peripheral Parenteral Nutrition (PPN): Fluids delivered through a smaller, peripheral vein in the neck or limbs. Used temporarily to provide partial parenteral nutrition.

5.3.4. Indications of TPN

TPN should be administered if the digestive system is not functioning properly or if the patient has a gastrointestinal disease that demands complete rest.

• Abdominal surgery
• Chemotherapy
• Intestinal ischemia, obstructions, or pseudo-obstruction
• Prolonged ileus
• Gastrointestinal bleeding
• Radiation enteritis
• Extremely premature birth
• Necrotising enterocolitis
• Prolonged diarrhoea
• Inflammatory bowel diseases
• Short bowel syndrome
• Persistent chyle leak
• Graft-versus-host disease of the gut

5.3.5. Administration of TPN

• TPN is administered through a central venous catheter—tunneled catheter (tube segment outside the skin) or implanted catheter (completely under the skin).
• The patient is anaesthetised, and the catheter is placed into a large vein that goes to the heart.
• Base solution (amino acids and dextrose) is prepared daily in a laminar flow hood in the hospital pharmacy. Minerals and vitamins are added.
• Starting dose: one litre of base solution per day. If tolerated, increase by 0.5-1 litre every day.
• While discontinuing TPN, gradually reduce the amount of glucose infused.

5.3.6. Benefits of TPN

• Provides the GI system a chance to heal from severe illness or surgery
• Helps geriatric patients manage nutrient requirements
• Can be life-saving for people with permanent GI dysfunction or extremely premature infants

5.3.7. Risks/Complications of TPN

• Bacterial infection: Sepsis may occur if infection spreads
• Blood clots: Can form at the catheter and vein meeting site
• GI atrophy: Occurs after 2 weeks
• Hyperglycaemia or hypoglycaemia: Treated with insulin and dextrose adjustments
• Parenteral Nutrition-Associated Liver Disease (PNALD): Complication of long-term use
• Gallbladder problems: Accumulation of bile without release
• Bone demineralisation: Osteoporosis or osteomalacia due to vitamin/mineral deficiencies

5.3.8. Contraindications of TPN

• When gastrointestinal feeding is permitted
• In infants with <8cm of small bowel
• In patients with metabolic or cardiovascular instabilities
• In patients with irreversibly decerebrate posture

Dpharmguru’s exam insights:

TPN is a frequently tested topic. Remember: TPN provides complete nutrition via IV route when the GI tract cannot be used. Macronutrients = proteins, calories (dextrose), fats. Micronutrients = vitamins, trace elements, electrolytes. Types = CPN (central vein) and PPN (peripheral vein). Complications include infection, blood clots, GI atrophy, hyperglycaemia, PNALD, and bone demineralisation. Know the indications and contraindications!

COMPARISON: TYPES OF IV ADMIXTURE INCOMPATIBILITIES

COMPARISON: CPN VS PPN

FREQUENTLY ASKED QUESTIONS (FAQs)

1. What is the difference between bulk compounding and IV admixture?

Bulk compounding is the large-scale production of non-commercially available drugs or modified formulations. IV admixture is the preparation of sterile products added to IV fluids for parenteral administration to individual patients. Bulk compounding is typically done for large quantities, while IV admixture is patient-specific.

2. What are the three types of IV admixture incompatibilities?

The three types are: Physical Incompatibility (visible changes like precipitation, colour change), Chemical Incompatibility (chemical degradation like hydrolysis, oxidation, photolysis), and Therapeutic Incompatibility (unwanted pharmacological effects like antagonism or synergism).

3. What is the difference between CPN and PPN?

CPN (Central Parenteral Nutrition) uses a central vein (superior vena cava) to deliver higher concentrations of nutrients for long-term/total nutrition. PPN (Peripheral Parenteral Nutrition) uses a smaller peripheral vein to deliver lower concentrations for short-term/partial nutrition.

4. What are the macronutrients in TPN?

The three macronutrients in TPN are: Proteins (amino acids), Calories (dextrose), and Fats (lipids). These provide the body with energy and essential nutrients when oral feeding is not possible.

5. What is the role of the pharmacist in IV admixture services?

The pharmacist provides permanent supervision, prepares protocols, advises on compatibility and stability, updates staff on guidelines, prevents incompatibilities, uses colour coding, prepares individual labelling, and ensures proper use of inline filters. The pharmacist is responsible for the safety and quality of IV admixtures.

6. What are the complications of long-term TPN use?

Complications include: bacterial infection (sepsis), blood clots, GI atrophy, hyperglycaemia/hypoglycaemia, Parenteral Nutrition-Associated Liver Disease (PNALD), gallbladder problems, and bone demineralisation (osteoporosis/osteomalacia).

SUMMARY

Compounding in hospitals is a critical pharmacy service that ensures patients receive medications tailored to their specific needs. Bulk compounding provides non-commercially available drugs and modified formulations through controlled manufacturing processes. Quality control, manufacturing process control, and budgetary control are essential for successful bulk compounding.

IV admixture services involve the preparation of sterile products added to IV fluids for parenteral administration. Physical, chemical, and therapeutic incompatibilities must be carefully monitored and prevented. The pharmacist plays a vital role in supervising IV admixture services, advising on compatibility, and ensuring patient safety.

Total Parenteral Nutrition (TPN) is a life-saving intervention for patients who cannot receive oral or enteral nutrition. Macronutrients (proteins, calories, fats) and micronutrients (vitamins, trace elements, electrolytes) must be carefully balanced based on individual patient needs. CPN and PPN offer different approaches based on the duration and concentration of nutrition required.

As I always tell my students: “Compounding is both an art and a science. It requires precision, attention to detail, and a deep understanding of pharmaceutical principles. Never compromise on quality control—a patient’s life may depend on it.”

REFERENCES AND FURTHER READING

• U.S. Food and Drug Administration (FDA). (2022). Compounding and Bulk Drug Substances. Retrieved from https://www.fda.gov.
• American Society of Health-System Pharmacists (ASHP). (2022). Guidelines on Compounding Sterile Preparations. Retrieved from https://www.ashp.org.
• World Health Organization (WHO). (2022). Good Manufacturing Practices for Pharmaceutical Products. Retrieved from https://www.who.int.
• Pharmacy Council of India (PCI). (2022). Hospital Pharmacy and Compounding Guidelines. New Delhi: PCI.
• United States Pharmacopeia (USP). (2022). USP Chapter <797>: Pharmaceutical Compounding – Sterile Preparations. Retrieved from https://www.usp.org.
• Allen, L. V., & Ansel, H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems (10th ed.). Wolters Kluwer Health.

Disclaimer: This article is for educational purposes only and does not constitute medical advice. Compounding practices and regulations may vary by region—always refer to your local regulatory authorities and pharmacopoeial standards for specific requirements.

written by:
Dr. N. Sujith Kumar

Dr. N. Sujith Kumar is a pharmacy educator, Pharm.D graduate, and academic content creator from Jawaharlal Nehru Technological University Kakinada (JNTUK), where he completed his Doctor of Pharmacy (Pharm.D) degree between 2015 and 2021. He has more than 7 years of experience creating pharmacy educational content, writing study materials, and reviewing academic articles for pharmacy students. He has also contributed guest articles to pharmacy education platforms, including PharmD Guru. At D.PharmGuru, his work focuses on simplifying complex Diploma in Pharmacy (D.Pharmacy) subjects into easy-to-understand notes, practical explanations, and exam-oriented educational resources for students across India. His areas of focus include Human Anatomy and Physiology, Pharmaceutics, Pharmacology, Pharmaceutical Chemistry, Hospital and Clinical Pharmacy, and other core D.Pharmacy subjects.

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